Herpes simplex virus type 1 and 2 10298 In the case of a herpes virus, initial interactions occur when a viral envelope glycoprotein called glycoprotein C (gC) binds to a cell surface particle called heparan sulfate. A second glycoprotein, glycoprotein D (gD), binds specifically to at least one of three known entry receptors. These include herpesvirus entry mediator(HVEM), nectin-1 and 3-O sulfated heparan sulfate. The receptor provides a strong, fixed attachment to the host cell. These interactions bring the membrane surfaces into mutual proximity and allow for other glycoproteins embedded in the viral envelope to interact with other cell surface molecules. HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia. HSV-1 tends to reside in the trigeminal ganglia, while HSV-2 tends to reside in the sacral ganglia, but note that these are tendencies only, not fixed behavior (Wiki: Herpes simplex virus). Herpes HSV evades the immune system through interference with MHC class I presentation of antigen on the cell surface. This is achieved through blockade of the TAP transporter induced by the secretion of ICP-47 by HSV. TAP maintains the integrity of the MHC class I molecule before it is transported via the golgi apparatus for recognition by CD8+ CTLs on the cell surface. ICP-47 disrupts this integrity, preventing the capture of cytosolic proteins for CTL recognition and thus evades CTL destruction (Wiki: Herpes simplex virus). HSV-1 and HSV-2 infect humans and mice are used as a model of protection in vaccine studies (Nass et al., 1998). Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as Human herpes virus 1 and 2 (HHV-1 and -2), are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and -2 are ubiquitous and contagious. They can be spread when an infected person is producing and shedding the virus. Symptoms of herpes simplex virus infection include watery blisters in the skin or mucous membranes of the mouth, lips or genitals. Lesions heal with a scab characteristic of herpetic disease. However, as neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body for the life of the carrier by becoming latent and hiding from the immune system in the cell bodies of nerves. After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the nerve's axon to the skin, where virus replication and shedding occur and cause new sores. There is no known cure for HSV infection, but treatments can reduce the likelihood of viral shedding and spread (Wiki: Herpes simplex virus). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 GSK1437173A Herpes Zoster vaccine GSK1437173A VO_0004598 Subunit vaccine Clinical trial Intramuscular injection (i.m.) AS01 (Chlibek et al., 2013) Intramuscular injection (i.m.) Glycoprotein E (gE) (Chlibek et al., 2013) Recombinant protein preparation Cell-mediated and humoral immune responses immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE. gE/AS01B induced stronger immune responses than gE/AS01E (Chlibek et al., 2013). This project was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline (Chlibek et al., 2013). VO_0003057 No vaccine-related severe adverse events were reported, and solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom (Chlibek et al., 2013). Herpes simplex virus 1 gD mutant vaccine KOS-gDA3C VO_0002970 Live, attenuated vaccine Research Flank scratch Flank scratch Gene mutation This gD mutant is from human herpesvirus 1 (Awasthi et al., 2008). A gD mutant is attenuated in mice (Awasthi et al., 2008). A gD mutant induces significant protection in mice from challenge with wild type HSV-1 (Awasthi et al., 2008). Herpes simplex virus 1 gH mutant vaccine VO_0002971 Live, attenuated vaccine Research Ear pinna Ear pinna Gene mutation This gH mutant is from Herpes simplex virus type 1 (Farrell et al., 1994). A gH mutant is attenuated in mice (Farrell et al., 1994). A gH mutant induces significant protection in mice from challenge with wild type HSV-1 (Farrell et al., 1994). Herpes simplex virus 1 TK mutant vaccine VO_0002973 Live, attenuated vaccine Research Intracerebral immunization Intracerebral immunization Gene mutation This TK mutant is from human herpesvirus type 1 (Field and Wildy, 1978). A TK mutant is attenuated in mice (Field and Wildy, 1978). A TK mutant induces significant protection from challenge with wild type HSV-1 (Field and Wildy, 1978). Herpes simplex virus 1 UL29 mutant vaccine VO_0002974 Live, attenuated vaccine Research subcutaneous injection subcutaneous injection Gene mutation This UL29 mutant is from human herpesvirus type 1 (Morrison and Knipe, 1994). A UL29 mutant is attenuated in mice (Morrison and Knipe, 1994). A UL29 mutant induces significant protection from challenge with wild type HSV-1 (Morrison and Knipe, 1994). Herpes Simplex Virus 2 DNA Vaccine encoding gD VO_0004522 DNA vaccine Research pDNAVACC [Ref2535:Tirabassi et al., 2011] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction The vaccine stimulated high titers of serum neutralising antibodies, a DNA priming dose dependent T helper type response, enhanced mucosal immune responses and potent protective immunity at the vaginal cavity, the portal of entry for the virus (Tirabassi et al., 2011). gD DNA vaccine or empty plasmid was administered intramuscularly on days 0 and 2. gD-liposomes or empty liposomes were administered 3 weeks after the DNA prime (50 μl total dose per mouse per time point in both nostrils) (Tirabassi et al., 2011). VO_0000286 The vaccine induced durable protection in mice, demonstrated by a 60% survival rate when lethal infections were performed 20 weeks after the immunisation primed with 0.5 μg of DNA vaccine (Tirabassi et al., 2011). The clinical isolate, HSV-2 strain MS was grown and titered in Vero cells. LD50 was titrated in Balb/c mice prior to the challenge experiments. Five days prior to infection, mice were injected subcutaneously with 2 mg of medroxyprogesterone. On the day of infection, animals were anesthetised intraperitoneally with a ketamine/xylazine mixture and instilled intravaginally with a 20 μl suspension containing the indicated virus dose (Tirabassi et al., 2011). Herpes Simplex Virus 2 DNA Vaccine encoding gD with CD40L VO_0004523 DNA vaccine Research pCDNA3-CD40L [Ref2536:Sin et al., 2001] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction When coinjected with CD40L plus pgD vaccines, a significant increase in Th cell-proliferative responses was observed. Specifically, CD40L drives immune responses toward a Th1 phenotype (Sin et al., 2001). The quadriceps muscles of BALB/c mice were injected with 10–60 mg of pgD DNA constructs formulated in a final volume of 100 ml of phosphate-buffered saline and 0.25% bupi- vacaine-HCl, using a 28-gauge needle. Forty micrograms of CD40 and CD40L gene expression cassettes was mixed with pgD plasmid solution prior to injection (Sin et al., 2001). VO_0000286 When mice were immunized with gD plasmid DNA and then challenged with 4 LD50, 60% survival of gD plasmid-vaccinated animals was noted. When covaccinated with CD40L, 100% of the challenged animals survived (Sin et al., 2001). After DNA injection, mice were challenged intravaginally with HSV-2 strain 186 with some modification. Before inoculating the virus, the intravaginal area was swabbed with a cotton-tipped applicator soaked with 0.1 M NaOH solution and then cleared with dried cotton applicators (Sin et al., 2001). Herpes Simplex Virus 2 DNA Vaccine Vaxfectin-gD2 VO_0004521 DNA vaccine Research VR1012 [Ref2534:Shlapobersky et al., 2012] Intravaginal injection Intravaginal injection DNA vaccine construction Both FL and S forms of gD2 formulated with Vaxfectin showed significantly higher antibody titres, compared with gD2 alone (Shlapobersky et al., 2012). VO_0000286 At a high viral challenge, the 0.1 µg dose of FL gD2 Vaxfectin-formulated pDNA yielded 80 % survival. In addition, 40 % of mice vaccinated with adjuvanted FL pDNA had no detectable HSV-2 viral genomes in the dorsal root ganglia (Shlapobersky et al., 2012). Herpes simplex virus 2 ICP0 mutant vaccine VO_0002972 Live, attenuated vaccine Research Vaginal immunization Vaginal immunization Gene mutation This ICP0 mutant is from Human herpesvirus type 2 (Halford et al., 2011). An ICP0 mutant is attenuated in mice (Halford et al., 2011). An ICP0 mutant induces protection in mice from challenge with wild type HSV-2 (Halford et al., 2011). Immunization with the live-attenuated HSV-2 0ΔNLS virus elicited a significant IgG antibody response directed against HSV-2's entry receptor, gD-2. gD-2 specific IgG antibodies were detected at levels significantly higher than levels detected in naive mice at day 50 after inoculation (Halford et al., 2011). Herpes simplex virus DNA vaccine ∆gB-2 encoding gB VO_0004366 DNA vaccine Research V1Jns [Ref2264:McClements et al., 1996] Intraperitoneal injection (i.p.) Intraperitoneal injection (i.p.) DNA vaccine construction Vector V1Jns expressed the hsV-2 gB gene (McClements et al., 1996). The DNA immunization has the capacity to elicit cell-mediated, as well as humoral immune responses. In addition, injection of mice showed that each construction induced neutralizing serum antibodies (McClements et al., 1996). VO_0000286 Immunized and control (saline-injected) mice were challenged by i.p. injection of HSV-2 and observed daily for survival. Significant protection from death was found for each dose tested (P< 0.01 for the 30, 10, and 3 ug groups, and P = 0.027 for the 1 ug group) (McClements et al., 1996). Herpes simplex virus DNA vaccine encoding gD and gB from HSV-2 strain Curtis VO_0004370 DNA vaccine Research V1Jns [Ref2267:McClements et al., 1997] Intramuscular injection (i.m.) Intramuscular injection (i.m.) gD and gB from HSV-2 strain Curtis (McClements et al., 1997) DNA vaccine construction Vector V1Jns expressed HSV envelope glycoproteins D (gD) (McClements et al., 1997). DNA vaccine construction Vector V1Jns expressed HSV envelope glycoprotein B (UL27) (McClements et al., 1997). Immunization with a plasmid expressing gB induced humoral immune responses and virus neutralization (McClements et al., 1997). VO_0000286 When the gB plasmid was combined with a plasmid expressing full-length gD, immunized guinea pigs developed humoral responses to both proteins and were also significantly protected from viral challenge. In addition, immunized animals were partially protected from genital herpes, exhibiting significantly reduced primary and subsequent recurrent disease (McClements et al., 1997). Herpes simplex virus DNA vaccine gB-DNA encoding gB VO_0004368 DNA vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction This DNA vaccine encodes glycoprotein B (gB) (Manickan et al., 1997). VO_0000286 The majority of mice immunized with plasmid DNA encoding gB resisted challenge with 10 ID50 of virus (Manickan et al., 1997). Herpes simplex virus DNA vaccine gBDNA encoding gB VO_0004369 DNA vaccine Research pIL-15 [Ref2266:Toka and Rouse, 2005]. intranasal immunization IL-15 (Toka and Rouse, 2005) intranasal immunization DNA vaccine construction This DNA vaccine expressed glycoprotein B of HSV (gBDNA) (Toka and Rouse, 2005). pIL-15 generated memory CD8 T cell responses that were threefold higher and mainly maintained in the spleen, but high levels of immunoglobulin A antibodies were induced and maintained long-term in the vaginal mucosa (Toka and Rouse, 2005). VO_0000286 The enhanced immune responses ensuing from this strategy of immunization were protective upon lethal challenge with HSV-1. Five out of six mice survived after challenge (Toka and Rouse, 2005). Herpes simplex virus DNA vaccine gD-2 encoding gD VO_0004365 DNA vaccine Research V1Jns [Ref2264:McClements et al., 1996] Intraperitoneal injection (i.p.) Intraperitoneal injection (i.p.) DNA vaccine construction Vector V1Jns expressed the HSV-2 gD gene (McClements et al., 1996). The DNA immunization has the capacity to elicit cell-mediated, as well as humoral immune responses. In addition, injection of mice showed that each construction induced neutralizing serum antibodies (McClements et al., 1996). VO_0000286 Immunized and control (saline-injected) mice were challenged by i.p. injection of HSV-2 and observed daily for survival. Significant protection from death (P< 0.001) was achieved for each dose. Eighty-two of eighty-six gD-2 DNA-immunized mice survived challenge (McClements et al., 1996). Herpes simplex virus DNA vaccine ICP-27 DNA encoding ICP-27 VO_0004367 DNA vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction This DNA vaccine expresses infectious cell polypeptide 27(ICP-27) (Manickan et al., 1997). DC-delivered DNA appeared to be associated mainly with an increased Thi CD4
T cell response (Manickan et al., 1997). VO_0000286 The majority of mice immunized with plasmid DNA encoding ICP 27 resisted challenge with 10 ID50 of virus (Manickan et al., 1997). Herpes simplex virus DNA vaccine pCI-gB encoding gB VO_0004412 DNA vaccine Research pCI [Ref2329:Hariharan et al., 1998] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pCI expressed glycoprotein B of herpes simplex virus type 1 (Hariharan et al., 1998). A single intramuscular immunization of BALB/c mice with pSIN vectors expressing the glycoprotein B of herpes simplex virus type 1 induced a broad spectrum of immune responses, including virus-specific antibodies, cytotoxic T cells, and protection from lethal virus challenge in two different murine models (Hariharan et al., 1998). VO_0000286 100% of the mice surviving the lethal i.p. McKrae challenge, demonstrating complete protection. None of the mice immunized with 100-μg doses of either negative control plasmid (pCI-HBVe or pSIN1.5-HBVe) survived (Hariharan et al., 1998). Herpes simplex virus DNA vaccine pSIN-gB encoding gB VO_0004411 DNA vaccine Research Sindbis virus-based (pSIN vectors) [Ref2329:Hariharan et al., 1998] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector Sindbis virus-based (pSIN vectors) expressed glycoprotein B of herpes simplex virus type 1 (Hariharan et al., 1998). A single intramuscular immunization of BALB/c mice with pSIN vectors expressing the glycoprotein B of herpes simplex virus type 1 induced a broad spectrum of immune responses, including virus-specific antibodies, cytotoxic T cells, and protection from lethal virus challenge in two different murine models (Hariharan et al., 1998). VO_0000286 100% of the mice surviving the lethal i.p. McKrae challenge, demonstrating complete protection. None of the mice immunized with 100-μg doses of either negative control plasmid (pCI-HBVe or pSIN1.5-HBVe) survived (Hariharan et al., 1998). Herpes Simplex Virus Type 1 DNA Vaccine encoding 5gP VO_0004520 DNA vaccine Research VR-1055 [Ref2532:Osorio et al., 2004] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction DNA vaccine construction DNA vaccine construction DNA vaccine construction DNA vaccine construction All immunized groups had significantly higher neutralizing antibody titers than mock-vaccinated mice (Osorio et al., 2004). The complete open reading frame for each of the five HSV-1 glycoproteins (gB, gC, gD, gE, and gI) was cloned into the VR-1055 expression vector and grown in bacteria. Plasmid DNA encoding each glycoprotein was purified on a cesium chloride gradient. In each experiment, 10 mice per group were inoculated intramuscularly (IM) into each quadriceps on days 0, 21, and 42 with a cocktail consisting of 10 μg of each cesium chloride–purified DNA (Osorio et al., 2004). VO_0000286 In all vaccine groups, 10 of 10 (100%) of the mice survived, whereas only 15 of 70 (21%) mock groups showed similar survival patterns after ocular infection (Osorio et al., 2004). Ocular challenge was performed 3 weeks after the final immunization. An inoculum of 2 × 105 or 2 × 106 pfu of HSV-1 strain McKrae in 5 μL tissue culture medium was placed in each eye without anesthesia and without corneal scarification, and the lid was gently rubbed for 30 seconds (Osorio et al., 2004). Herpes simplex virus type 1 DNA vaccine encoding GC VO_0011408 DNA vaccine Research pRc/CMV Herpes simplex virus type 1 envelope glycoprotein C DNA vaccine construction The HSV-1 KOS gC gene was isolated by PCR. Each gene was initially cloned into a TA cloning vector and then into a eukaryotic plasmic expression vector that uses the cytomegalovirus immediate-early promoter for expression (pRc/CMV for gC) (Nass et al., 1998). BALB/c Groups of 5 BALB/cByJ mice received 100-uL injections of purified plasmids into the quadriceps muscles of the hind legs. In most cases, injections were 3 weeks apart; blood samples were taken from the tail vein 1 day before injection or challenge, and approximately equal volumes of blood from individual mice were pooled within a group (Nass et al., 1998). Protection against a lethal intraperitoneal challenge of HSV-1 (5 x 10^4 pfu) with gC (UL44) or gE plasmid vaccination could be demonstrated if the inoculating dose of DNA was 250 microg. All mice immunized with vaccinia recombinants expressing either gC or gE survived HSV-1 challenge (Nass et al., 1998). Three weeks after the final injection, mice were challenged ip with 5 x 10^4 pfu of HSV-1 McKrae, which was ~10 LD50S, as determied in BALB/cByJ mice (Nass et al., 1998). Herpes simplex virus type 1 DNA vaccine encoding GD VO_0011421 DNA vaccine Research pcDNA3 Intradermal injection (i.d.) Intradermal injection (i.d.) Herpes simplex virus type1 glycoprotein D DNA vaccine construction Plasmid DNA encoding HSV-1 glycoprotein D1 (gD1) was constructed by insertion of the gD1 gene into pcDNA3 (Jamali et al., 2009). BALB/c BALB/c mice were immunized three times intra-dermally with 50 µg of pcDNA3 gD1 in a total volume of 100 µl on days 0, 21 and 42 (gD1 group). NLX (Sigma) was dissolved in 100 µl PBS containing 50 µg of the pcDNA3 gD1 construct at a concentration of 5 mg kg–1 and injected to each mouse with the same protocol, i.e. NLX was administered intra-dermally in combination with the pcDNA3 gD1 on days 0, 21 and 42 (NLX-gD1 group). PBS was injected according to the same protocol into the third group of mice as a negative control (PBS group). Finally, the last control group of mice was inoculated according to the same protocol with 100 µl of inoculums containing 10^5 plaque-forming units (pfu) of KOS strain virus (KOS group) (Jamali et al., 2009). BALB/c mice receiving a glycoprotein D1 (gD1, US5) DNA vaccine alone were 80% protected against a subsequent HSV-1 challenge. Results also indicate that the administration of NLX as an adjuvant improved protective immunity against HSV-1 (Jamali et al., 2009). Three weeks after the last immunization, mice were challenged with a low dose [four mouse lethal dose fifty percent (MLD50) = 1 x 10^5 pfu] or a high dose (10 MLD50 = 1 x 10^5 pfu) of wild-type virus. The mortality rate was followed for 2 weeks (Jamali et al., 2009). Herpes simplex virus type 1 DNA vaccine encoding GE VO_0011423 DNA vaccine Research pRc/CMV Herpes simplex virus type 1 glycoprotein E DNA vaccine construction The HSV-1 KOS gE gene was isolated by PCR. Each gene was initially cloned into a TA cloning vector and then into a eukaryotic plasmic expression vector that uses the cytomegalovirus immediate-early promoter for expression (pRc/CMV for gE) (Nass et al., 1998). BALB/c Groups of 5 BALB/cByJ mice received 100-uL injections of purified plasmids into the quadriceps muscles of the hind legs. In most cases, injections were 3 weeks apart; blood samples were taken from the tail vein 1 day before injection or challenge, and approximately equal volumes of blood from individual mice were pooled within a group (Nass et al., 1998). Protection against a lethal intraperitoneal challenge of HSV-1 (5 x 10^4 pfu) with gC or gE (US8) plasmid vaccination could be demonstrated if the inoculating dose of DNA was 250 microg. All mice immunized with vaccinia recombinants expressing either gC or gE survived HSV-1 challenge (Nass et al., 1998). Three weeks after the final injection, mice were challenged ip with 5 x 10^4 pfu of HSV-1 McKrae, which was ~10 LD50S, as determied in BALB/cByJ mice (Nass et al., 1998). Herpes Simplex Virus Type 1 DNA Vaccine pRSC-gD-IL-21 VO_0004519 DNA vaccine Research Eye-drop immunization Eye-drop immunization DNA vaccine construction The nanoparticles containing DNA vaccine pRSC-gD-IL-21 induced mice to generate higher levels of specific neutralizing antibody, sIgA in tears, and IFN-γ, IL-4 in serum (Hu et al., 2011). For the vaccination experiments, Balb/c mice were randomly divided into pRSC-group (mock plasmid), pRSC-gD group, pRSC-gD-IL-21 group and pRSC-gD-IL-21+ nanoparticles group in order. 12 mice per group were used routinely. In the nanoparticles group, 20 μl (40 μg DNA) of the nanoparticles containing DNA vaccine pRSC-gD-IL-21 were topically dropped into the eye of each mouse on days 0, 14 and 28. In other groups, each mouse was inoculated topically into the eye with 40 μg DNA vaccine pRSC-gD-IL-21 or pRSC-gD or mock plasmid in 20 μl PBS 3 times at two week intervals (Hu et al., 2011). VO_0000286 On day 10 after viral challenge, there was no keratitis in the mouse of the pRSC-gD-IL-21+ nanoparticles group, demonstrating that the pRSC-gD-IL-21+ nanoparticles vaccine was efficient to inhibit HSK in a mouse model (Hu et al., 2011). Three weeks after the final immunization, 6 mice per group were sacrificed and used for detecting immune efficiency, and the other 6 mice were used for HSV-1 challenge experiments. Mice were anesthetized by intraperitoneal injection of sodium pentobarbital (1.5 mg/0.15 ml) and the corneas of mice were scarified 10 times with 1 ml needle and the ocular mucosa of each eye were dropped with HSV-1 (10 μl of 5 × 106 plaque forming unit (PFU)/ml) (Hu et al., 2011). Herpes simplex virus type 2 DNA vaccine encoding GB VO_0011406 DNA vaccine Research cytomegalovirus promoter (pCI) Intranasal Intranasal Herpes simplex virus type 2 glycoprotein B (UL27) DNA vaccine construction The plasmid DNA used for immunization was purified by polyethylene glycol precipitation. Briefly, the cellular proteins were precipitated with 1 volume of 7.5 M ammonium acetate. The supernatant was then precipitated with isopropanol, after which the plasmids were extracted three times with phenol-chloroform and then precipitated with pure ethanol. The DNA quality was then checked by electrophoresis in 1% agarose gel. Next, the concentration of the plasmid DNA was measured using a GeneQuant RNA/DNA calculator (Biochrom, Cambridge, UK). The amount of endotoxin was then determined using the Limulus amebocyte lysate (LAL) test (< 0.05 EU/µg) (Kim et al., 2009). BALB/c Groups of 5- to 6-week old female mice (n = 7) were co-immunized intranasally (i.n.) with 100 µg of pCIgB in the presence of β2-adrenergic agonist, salbutamol (10, 50, 100, and 200 µg). To examine the effect of plasmid DNA backbone (e.g. CpG motif), some of mice were immunized i.n. with 100 µg of the control vector (pCI-neo) in parallel. The i.n. immunization was performed three times at 7-day intervals (days 0, 7, and 14) by depositing pCIgB dissolved in a total volume of 20 µl of PBS (pH 7.2) containing the indicated dose of salbutamol onto the nares of deeply anesthetized mice (Kim et al., 2009). The present study evaluated the modulatory functions of salbutamol co-administered with DNA vaccine expressing gB (UL27) of herpes simplex virus (HSV) via intranasal (i.n.) route. The enhanced immune responses caused by co-administration of salbutamol provided effective and rapid responses to HSV mucosal challenge, thereby conferring prolonged survival and reduced inflammation against viral infection (Kim et al., 2009). BALB/c mice were subcutaneously injected with Depo-Provera (DP) (Upjohn Co., Kalamazoo, MI) at 2 mg per mouse. Five days following the injection of DP, the mice were challenged intravaginally with 10^6 PFU of HSV-1 McKrae. The mice were examined daily for vaginal inflammation, neurological illness, and death (Kim et al., 2009). Herpes simplex virus type 2 DNA vaccine encoding ICP27 VO_0011405 DNA vaccine Research pTarget, and a plasmid vector encoding the A and B subunits of the Escherichia coli heat labile enterotoxin (LT) Herpes simplex virus type 2 transcriptional regulator ICP27 DNA vaccine construction The plasmid-encoding HSV-2 ICP27 was generated by inserting a PCR fragment incorporating the entire ICP27 gene (UL54) into pTarget (Promega, Madison, WI) (Haynes et al., 2006). BALB/c Each immunization of 6–8-week-old female Balb/c mice consisted of a single PMED™ delivery to the ventral abdominal skin in which each delivery contained 0.5 mg of gold coated with a total of 0.5 μg of the DNA vaccine-DEI vector formulation. Two such “single shot” immunizations were administered 4 weeks apart and animals were sacrificed or challenged 2 weeks following the second immunization (Haynes et al., 2006). Particle-mediated DNA vaccination of mice with a DNA plasmid-encoding ICP27 resulted in the induction of ICP27-specific IFN-gamma and TNF-alpha production in Balb/c mice. When the DNA vaccine was supplemented with as little as 50ng of a vector encoding the A and B subunits of the Escherichia coli heat labile enterotoxin (LT), animals were profoundly protected from morbidity and mortality (Haynes et al., 2006). Anesthetized Balb/c mice were intranasally challenged with 30 μl of PBS containing approximately 50 LD50 (2 × 10^6 PFU) of HSV-2 strain MS. Mice were followed for 20 days after infection and scored for morbidity and mortality (Haynes et al., 2006). Herpes simplex virus type 2 vaccine using phage displaying GG protein VO_0011420 Recombinant vector vaccine Research Filamentous phage Subcutaneous injection Subcutaneous injection Herpes simplex virus type 2 envelope glycoprotein G (US4) Recombinant protein preparation Phage clones were isolated that express peptides that mimic single epitopes of the glycoprotein G of HSV-2, gG2 (Grabowska et al., 2000). BALB/c BALB/c mice were obtained from a randomly bred, closed colony at the Sheffield University animal facility. Immunisations were administered subcutaneously at 2-week intervals. The dose given is the quantity of phage used per mouse per immunisation in a 200 ml volume of TBS. Prebleeds were obtained from a random selection of the mice prior to immunisation, and further bleeds were taken from all mice 2 weeks after each immunisation (Grabowska et al., 2000). In two experiments, mice immunised with phage displaying a single epitope of gG2 (US4) were protected against challenge with a lethal dose of whole HSV-2 (Grabowska et al., 2000). Four weeks after the last immunisation, mice were challenged with 5±6 mouse lethal doses of HSV-2 (strain 333). Survival of the mice was monitored daily (Grabowska et al., 2000). HSV 2 DNA vaccine pVAX–HSV–2gD–Hsp70 VO_0004578 DNA vaccine Research pVAX [Ref2710:Fan and Yang, 2010] Intramuscular injection (i.m.) Intramuscular injection (i.m.) HSV–2gD gene fragment and Tubercle bacillus Hsp70 gene (Fan and Yang, 2010) DNA vaccine construction The IgG response in serum in vaccinated mice with pVAX–HSV–2gD and pVAX–HSV–2gD–Hsp70 differed significantly (P < 0.05) from those in immunized mice with pVAX and pVAX–Hsp70, which did not generate antibody levels above background. The highest IgG concentration was observed in serum of mice immunized with pVAX–HSV–2gD–Hsp70, which showed significant differences compared with the other three groups (P < 0.05) (Fan and Yang, 2010). VO_0003057 Eight of the animals (8/10) have survived in group pVAX–HSV–2gD–Hsp70. Only one survived in the pVAX and pVAX–Hsp70 groups (Fan and Yang, 2010). HSV glycoproteins subunit vaccine VO_0004267 Subunit vaccine Research not specified not specified gB2t + gD2t (Burke et al., 1994) licensed Herpes simplex virus infection human vaccine Generic Unknown VO_0012168 Subunit vaccine Licensed A generic representation of vaccines utilized to prevent herpes simplex virus infection in humans, typically based on purified viral proteins such as glycoprotein subunits. These vaccines aim to elicit protective immune responses without using live virus. pRP-RSV-HSV-1-gB VO_0004723 Recombinant vector vaccine Research Intramuscular injection (i.m.) The herpes simplex virus type 1 (HSV-1) glycoprotein B (gB-1) gene, deleted of 639 nucleotides that encode the transmembrane anchor sequence and reconstructed with the extramembrane and intracytoplasmic domains, was cloned under control of the Rous sarcoma virus long terminal repeat in the episomal replicating vector pRP-RSV (Manservigi et al., 1990). Intramuscular injection (i.m.) Recombinant vector construction The herpes simplex virus type 1 (HSV-1) glycoprotein B (gB-1) gene, was cloned under control of the Rous sarcoma virus long terminal repeat in the episomal replicating vector pRP-RSV (Manservigi et al., 1990). Mice were immunized with secreted gB-1 produced HSV-1- and HSV-2-neutralizing antibodies (Manservigi et al., 1990). VO_0003057 Mice immunized with secreted gB-1 produced HSV-1- and HSV-2-neutralizing antibodies and were protected against HSV-1 lethal, latent, and recurrent infections (Manservigi et al., 1990). Mice were challenged with HSV-1 or LV (Manservigi et al., 1990). rOka-gD2- HSV-2 VO_0004710 Recombinant vector vaccine Research Intramuscular injection (i.m.) Herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome (Heineman et al., 1995). Intramuscular injection (i.m.) Recombinant vector construction The herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome (Heineman et al., 1995). The guinea pigs were inoculated with three doses of uninfected human fibroblasts, fibroblasts infected with ROka VZV, or fibroblasts infected with ROka-gD2 (Heineman et al., 1995). VO_0003057 Inoculation of guinea pigs with ROka-gD2 significantly reduced the severity of primary HSV-2 infection (P < 0.001). These experiments demonstrate that the Oka strain of VZV can be used as a live virus vector to protect animals from disease with a heterologous virus (Heineman et al., 1995). The guinea pigs were challenged intravaginally with HSV-2 (Heineman et al., 1995). gB Human herpesvirus 1 strain KOS 1353200 CDD:223014 10306 ? Envelope glycoprotein B 7.97 94956.45 1006 gB >sp|P06437.2|GB_HHV1K RecName: Full=Envelope glycoprotein B; Short=gB; Flags: Precursor MHQGAPSWGRRWFVVWALLGLTLGVLVASAAPTSPGTPGVAAATQAANGGPATPAPPPLGAAPTGDPKPK KNKKPKNPTPPRPAGDNATVAAGHATLREHLRDIKAENTDANFYVCPPPTGATVVQFEQPRRCPTRPEGQ NYTEGIAVVFKENIAPYKFKATMYYKDVTVSQVWFGHRYSQFMGIFEDRAPVPFEEVIDKINAKGVCRST AKYVRNNLETTAFHRDDHETDMELKPANAATRTSRGWHTTDLKYNPSRVEAFHRYGTTVNCIVEEVDARS VYPYDEFVLATGDFVYMSPFYGYREGSHTEHTTYAADRFKQVDGFYARDLTTKARATAPTTRNLLTTPKF TVAWDWVPKRPSVCTMTKWQEVDEMLRSEYGGSFRFSSDAISTTFTTNLTEYPLSRVDLGDCIGKDARDA MDRIFARRYNATHIKVGQPQYYQANGGFLIAYQPLLSNTLAELYVREHLREQSRKPPNPTPPPPGASANA SVERIKTTSSIEFARLQFTYNHIQRHVNDMLGRVAIAWCELQNHELTLWNEARKLNPNAIASVTVGRRVS ARMLGDVMAVSTCVPVAADNVIVQNSMRISSRPGACYSRPLVSFRYEDQGPLVEGQLGENNELRLTRDAI EPCTVGHRRYFTFGGGYVYFEEYAYSHQLSRADITTVSTFIDLNITMLEDHEFVPLEVYTRHEIKDSGLL DYTEVQRRNQLHDLRFADIDTVIHADANAAMFAGLGAFFEGMGDLGRAVGKVVMGIVGGVVSAVSGVSSF MSNPFGALAVGLLVLAGLAAAFFAFRYVMRLQSNPMKALYPLTTKELKNPTNPDASGEGEEGGDFDEAKL AEAREMIRYMALVSAMERTEHKAKKKGTSALLSAKVTDMVMRKRRNTNYTQVPNKDGDADEDDL Protective antigen gD 19548971 1L2G CDD:177571 CDD:186820 10298 ? glycoprotein D 394 envelope glycoprotein D; Provisional >gi|19548971|gb|AAL90884.1|AF487902_1 glycoprotein D [human herpesvirus 1] MGGAAARLGAVILFVVIVGLHGVRGKYALADASLKMADPNRFRGKDLPVLDQLTDPPGVRRVYHIQAGLP NPFQPPSLPITVYYAVLERACRSVLLNAPSEAPQIVRGASEDVRKQPYNLTIAWFRMGGNCAIPITVMEY TECSYNKSLGACPIRTQPRWNYYDSFSAVSEDNLGFLMHAPAFETAGTYLRLVKINDWTEITQFILEHRA KGSCKYTLPLRIPPSACLSPQAYQQGVTVDSIGMLPRFIPENQRTVAVYSLKIAGWHGPKAPYTSTLLPP ELSETPNATQPELAPEDPEDSALLEDPVGTVAPQIPPNWHIPSIQDAATPYHPPATPNNMGLIAGAVGGS LLAALVICGIVYWMHRRTRKAPKPIRLPHIREDDQPSSHQPLFY Virmugen KOS-gDA3C is attenuated with mutations in gD gene in causing skin lesions at the inoculation and zosteriform sites, yet it is as effective as rKOS-gDA3C in protecting mice against HSV-1 challenge [Ref1795:Awasthi et al., 2008]. gD Human herpesvirus 2 1487358 9629336 HHV2gp69 AY779751 NP_044536 10310 141015 143591 + envelope glycoprotein D 7.84 40611.38 393 gD family >gi|9629267:141015-143591 Human herpesvirus 2, complete genome CATGGGGCGTTTGACCTCCGGCGTCGGGACGGCGGCCCTGCTAGTTGTCGCGGTGGGACTCCGCGTCGTC TGCGCCAAATACGCCTTAGCAGACCCCTCGCTTAAGATGGCCGATCCCAATCGATTTCGCGGGAAGAACC TTCCGGTTTTGGACCAGCTGACCGACCCCCCCGGGGTGAAGCGTGTTTACCACATTCAGCCGAGCCTGGA GGACCCGTTCCAGCCCCCCAGCATCCCGATCACTGTGTACTACGCAGTGCTGGAACGTGCCTGCCGCAGC GTGCTCCTACATGCCCCATCGGAGGCCCCCCAGATCGTGCGCGGGGCTTCGGACGAGGCCCGAAAGCACA CGTACAACCTGACCATCGCCTGGTATCGCATGGGAGACAATTGCGCTATCCCCATCACGGTTATGGAATA CACCGAGTGCCCCTACAACAAGTCGTTGGGGGTCTGCCCCATCCGAACGCAGCCCCGCTGGAGCTACTAT GACAGCTTTAGCGCCGTCAGCGAGGATAACCTGGGATTCCTGATGCACGCCCCCGCCTTCGAGACCGCGG GTACGTACCTGCGGCTAGTGAAGATAAACGACTGGACGGAGATCACACAATTTATCCTGGAGCACCGGGC CCGCGCCTCCTGCAAGTACGCTCTCCCCCTGCGCATCCCCCCGGCAGCGTGCCTCACCTCGAAGGCCTAC CAACAGGGCGTGACGGTCGACAGCATCGGGATGCTACCCCGCTTTATCCCCGAAAACCAGCGCACCGTCG CCCTATACAGCTTAAAAATCGCCGGGTGGCACGGCCCCAAGCCCCCGTACACCAGCACCCTGCTGCCGCC GGAGCTGTCCGACACCACCAACGCCACGCAACCCGAACTCGTTCCGGAAGACCCCGAGGACTCGGCCCTC TTAGAGGATCCCGCCGGGACGGTGTCTTCGCAGATCCCCCCAAACTGGCACATCCCGTCGATCCAGGACG TCGCGCCGCACCACGCCCCCGCCGCCCCCAGCAACCCGGGCCTGATCATCGGCGCGCTGGCCGGCAGTAC CCTGGCGGTGCTGGTCATCGGCGGTATTGCGTTTTGGGTACGCCGCCGCGCTCAGATGGCCCCCAAGCGC CTACGTCTCCCCCACATCCGGGATGACGACGCGCCCCCCTCGCACCAGCCATTGTTTTACTAGAGGAGTT TCCCCGCTCCCGTGTACCTCTGGGCCCGTGTGGGAGGGTGGCTGGGGTATTTGGGTGGGACTTGGACTCC GCATAAAGGGAGTCTCGAAGGAGGGAAACTAGGACAGTTCATAGGCCGGGAGCGTGGGGCGCGCACCGCT GTCCCGACGATTAGCCACCGCGCCCACAGCCACCTCGACCCGTCCGATCCCGGTATGCCCGGCCGCTCGC TGCAGGGCCTGGCGATCCTGGGCCTGTGGGTCTGCGCCACCGGCCTGGTCGTCCGCGGCCCCACGGTCAG TCTGGTCTCAGACTCACTCGTGGATGCCGGGGCCGTGGGGCCCCAGGGCTTCGTGGAAGAGGACCTGCGT GTTTTCGGGGAGCTTCATTTTGTGGGGGCCCAGGTCCCCCATACAAACTACTACGACGGCATCATCGAGC TGTTTCACTACCCCCTGGGGAACCACTGCCCCCGCGTTGTACACGTGGTCACACTGACCGCATGCCCCCG CCGCCCCGCCGTGGCGTTCACCTTGTGTCGCTCGACGCACCACGCCCACAGCCCCGCCTATCCGACCCTG GAGCTGGGTCTGGCGCGGCAGCCGCTTCTGCGGGTTCGAACGGCAACGCGCGACTATGCCGGTCTGTATG TCCTGCGCGTATGGGTCGGCAGCGCGACGAACGCCAGCCGGTTTGTTTTGGGGGTGGCGCTCTCTGCCAA CGGGACGTTTGTGTATAACGGCTCGGACTACGGCTCCTGCGATCCGGCGCAGCTTCCCTTTTCGGCCCCG CGCCTGGGACCCTCGAGCGTATACACCCCCGGAGCCTCCCGACCCACCCCTCCACGGACAACGACACCCC CGTCCTCCCCCCGAGACCCGACCCCCGCCCCCGGGGACACAGGGACGCCCGCGCCCGCGAGCGGCGAGAT AGCCCCGCCCAATTCCACGCGATCGGCCAGCGAATCGAGACACAGGCTAACCGTAGCCCAGGTAATCCAG ATCGCCATACCGGCGTCCATCATCGCCTTTGTGTTTCTGGGCAGCTGTATCTGCTTCATCCATAGATGCC AGCGCCGATACAGGCGCCCCCGCGGCCAGATTTACAACCCCGGGGGCGTTTCCTGCGCGGTCAACGAGGC GGCCATGGCCCGCCTCGGAGCCGAGCTGCGATCCCACCCAAACACCCCCCCCAAACCCCGACGCCGTTCG TCGTCGTCCACGACCATGCCTTCCCTAACGTCGATAGCTGAGGAATCGGAGCCAGGTCCAGTCGTGCTGC TGTCCGTCAGTCCTCGGCCCCGCAGTGGCCCGACGGCCCCCCAAGAGGTCTAGGTCCAAGCGGGCCGTTC GGCAGGCCCGCCCCACCGCCCCCATCGTGGTTATTTCCCCCCCCCCCCCCCCAATAA >gi|9629336|ref|NP_044536.1| envelope glycoprotein D [Human herpesvirus 2] MGRLTSGVGTAALLVVAVGLRVVCAKYALADPSLKMADPNRFRGKNLPVLDQLTDPPGVKRVYHIQPSLE DPFQPPSIPITVYYAVLERACRSVLLHAPSEAPQIVRGASDEARKHTYNLTIAWYRMGDNCAIPITVMEY TECPYNKSLGVCPIRTQPRWSYYDSFSAVSEDNLGFLMHAPAFETAGTYLRLVKINDWTEITQFILEHRA RASCKYALPLRIPPAACLTSKAYQQGVTVDSIGMLPRFIPENQRTVALYSLKIAGWHGPKPPYTSTLLPP ELSDTTNATQPELVPEDPEDSALLEDPAGTVSSQIPPNWHIPSIQDVAPHHAPAAPSNPGLIIGALAGST LAVLVIGGIAFWVRRRAQMAPKRLRLPHIRDDDAPPSHQPLFY Other gH 138315 CDD:177579 10299 ? Envelope glycoprotein H 838 envelope glycoprotein H; Provisional >gi|138315|sp|P06477.1|GH_HHV11 RecName: Full=Envelope glycoprotein H; Short=gH; Flags: Precursor MGNGLWFVGVIILGVAWGQVHDWTEQTDPWFLDGLGMDRMYWRDTNTGRLWLPNTPDPQKPPRGFLAPPD ELNLTTASLPLLRWYEERFCFVLVTTAEFPRDPGQLLYIPKTYLLGRPPNASLPAPTTVEPTAQPPPSVA PLKGLLHNPAASVLLRSRAWVTFSAVPDPEALTFPRGDNVATASHPSGPRDTPPPRPPVGARRHPTTELD ITHLHNASTTWLATRGLLRSPGRYVYFSPSASTWPVGIWTTGELVLGCDAALVRARYGREFMGLVISMHD SPPVEVMVVPAGQTLDRVGDPADENPPGALPGPPGGPRYRVFVLGSLTRADNGSALDALRRVGGYPEEGT NYAQFLSRAYAEFFSGDAGAEQGPRPPLFWRLTGLLATSGFAFVNAAHANGAVCLSDLLGFLAHSRALAG LAARGAAGCAADSVFFNVSVLDPTARLQLEARLQHLVAEILEREQSLALHALGYQLAFVLDSPSAYDAVA PSAAHLIDALYAEFLGGRVLTTPVVHRALFYASAVLRQPFLAGVPSAVQRERARRSLLIASALCTSDVAA ATNADLRTALARADHQKTLFWLPDHFSPCAASLRFDLDESVFILDALAQATRSETPVEVLAQQTHGLAST LTRWAHYNALIRAFVPEASHRCGGQSANVEPRILVPITHNASYVVTHSPLPRGIGYKLTGVDVRRPLFLT YLTATCEGSTRDIESKRLVRTQNQRDLGLVGAVFMRYTPAGEVMSVLLVDTDNTQQQIAAGPTEGAPSVF SSDVPSTALLLFPNGTVIHLLAFDTQPVAAIAPGFLAASALGVVMITAALAGILKVLRTSVPFFWRRE Virmugen A gH mutant is attenuated in mice and induces significant protection from challenge with wild type HSV-1 [Ref1867:Farrell et al., 1994]. ICP0 Human herpesvirus 2 1487289 109676722 HHV2gp61 Z86099 NP_044528 10310 121626 124946 - ubiquitin E3 ligase ICP0 8.18 77292.34 824 >gi|9629267:121626-124946 Human herpesvirus 2, complete genome CTTTATTGTAAAATTTTTATAAATATAAAGTTTTTTTTTTCCTCAAGTTTTCAACAAGGCCAGAAAGTCC ATAACAAAATGCTGGTGTGTGTTGCTGTTCGGGGCCGTGTCCGTCCCCCCCCCCCACTCCCACCCCCACT TCCTGTCTCCTCCCCGTCTTTCCCCCCCCCCACCTCCCCCTGCCCCCGAGGCGCCTCGGCCGGTGGTCCG GTGGGGGGCGGCTTCCTTCGGGCAGCAAGCCGAGTGTTAGCTCCCCCTACTCCCCGTGGCCCGCGGGGGC GTCGCCGGCCGGCGCGGGCGCGCCCTGCTCCCGAGACCACGGGTGGCGCGACCGGAGGCCGTGGAAGTCC AGCGCGCCCACCAGGGTGCCCTGGTCAAAGAGCATGTTGCCCACCGGGGTCATCCAGAGGCTGTTCCACT CCGACGCGGGGGGCGTCGGGTAGTCGGGGGGCCTCACGCAGTTGCGCGCGTGCTCGGGGAGCAGGGTGCG GCGGCTCCACGCGGGGGCCGCGGCCCGCAGCAGGTCCGCCACGTTCCCCGTCTGGTCCACGAGGACCACG TAGGCCCCTATGTGGCCCGTCTCCATGTCCAGGACGGGCAGGCAGTCCCCCGTGACCGTCTTGTTCACGT AAGGCGCCAGGGCCACGACGCTCGAGACCCCCGCGATGGGCAGGTAGCGCGTGAGGCCGGGCGCCGGGTC GCGGGCCCCGGGCTCGGGGCCGCCCTCCGCGTGGCGCGTCTTCCTGGCACACTTCCTCGGCCCCCGCGGC GCAGCAGCGCGGGGGCCGAGGGAGGTTTCTCGTCTCTCCCCAGCGCCGGACGCGGACGCGACGCTCCCAC CAGCCCCGCCCGCAGAGGAAGAGGCGGAGGAGGAGGAGGCGGAGGAGGAGGAGGCGGAGGAGGAGGAGGC GGAGGAGGAGGAGGCGGAGGAGGAGGAGGCGGAGGAGGAGGAGGCGGAGGAGGAGGAGGCGGCGGCGACC GCGGCCTGGGACGACGGAGACGCCGACGGGGGCGCGGCGCCCGCGGACGCCGGGGCGAGCGGCCCGTGGC CGCGGTCGCCCGAGTCCGAGTCCGGGGCCCGGCGCGGCGCCGCCCTCTTGGCCCCCACCCCCTGGGGGGC GAGGGGCGAGCGCGGGGCGGCGGAGGAAGAGGCGGAGGACGAGGCCGCGGGGCCCGAGTCCGACCCGCGC CTCTTCCGGGGGCGGGCCGCCGCCCCCTCCGCGGCGTGGGGGGCGGCACCGGGGGTGTTGGTGCCGCGGG GGACCCCGGGTCCTCCCTCCGCGCCCGGCCCTCCCGACCCGCGCGCGTCGGTCGCGCCTGCCCGGCCCAG ACTCTGTGCTTGGGTGTCGGTCTGAGCCTGGGTCATGCGCGACCGGGGCGCGCGGTGCGCGTCCACCGGC ACGGCGGGCGGCGCGGGCCCGGCCGCGTCCGCGCTCGCAGACACCACGGGGGCGGCGGCGGCGCGGGGCG GACTCCGGACGCGCGGGGCGACGGCCGCGCGGGGGCGCGCGGCGCGCCCCGACGACTGTGGCAGACCTCC CCCCCCGGGGCCCGAGGACACCTGTGCGGAGGAGGAGGAGACAAAGGAGAGCGGCCCGGGGCCCGCGGGG CGGCGCGGAGACGGCGGGGGAGAGTCGCTGATGACTATGGGGGGCTCCTGGGCCGCGCGGGGCTGTCTCG CGGGGGGCGTCCTGCCCTCCGCCGCCGCGGCGTCTTCGCCCACCCGCCGCGCCTGCGCGCGCCCCCCGCC GGCCGCAGGGGGAAGAGAGGCCACTCTCGGCACGACGGCCGCGACGGCAGGGCCGCCCCCAGACCCAGAT CCCACCCCCGCCCGCAACGGGGCGCCGCCGCTGCTGCTGCTCCGCGGGGCGCCAGGGGGCGCCGGTCGGG TCGCGGCGGGCTGGGAGGTTCCGCGGGTCGCCCCCGCACCGCCGCCCCCGCGCCGGGGCGCTCTTCGGGG GGCGGGCGGGACGTAGTCCACTGCAGAGGGAGACAGAGACGGGAGCCCCCGGTTAGTGCCCGACCCCCGC CCGACCCCCGCCCGACCCCCGCCCGACCCCCGCCCGACCCCCGCCCGACCCCCGCCCGACCCCCGCCCGA CCCCCGCCCGACCCCCGCCCGACCCCCGCCCGCCCCCCGCCCGACCCCCGCCCGCCCTCACCGTCGGCCA GGTCATCGTCCTCGTCGTCCGTGCCGGGCCACGGGGGGGTGGGCGACAGGGCGCGGACCGTGTGTCCCCC CAGCGACAGGGAGCGCGGGGCCGTCCGCGGGTTGCCCGTCCAGATAAAGTCCACGGCCGTGCCGGCCCGC ACGGCCGCCTCGGCCTCCACGCGGGTCCGGGGGTCGTTCACTATCGGGATGGTGCTGAACGACCCGCTGG CGGTCACGCCCACTATCAGGTACGCCACCGGGGTGTTGCACAGGGGACACGTGTTGCGCAACGGAATCCA GGTCTTCATGCACGGGATGCAGAAGGGGTGCAGGCAGGGAAAACTCTGGCAGCGCAGGGGCGGGGCGATC TCGTCCGTGCACACGGCACACACGTCGCCCCCCCCTCCCGCTTCCGCTTCCTCCTCACCCACGGGCCCAC CCCCACAGGATCCCTGCGCGTCGGCGGGCGTGGGGCTGCCCTGGCGCTCGGCCGGGGGCCGGGCCGGGGG CGTGGCCGCGTCCATCAGGCCCGCCTCGAACATCTCCGTGTCCGTGCTGCCCGCCTCGGAGGTGGAGTCG CGGTGAAGGTCGTCGTCAGAGATTCCCACCTCGGTCTCCTCCTCCGAGTCGCTGCTGGCGAGCCACTGCA TGTCGTTGAGCATCCCCCAGGCGTGCGGGGCGGCGGGCTGCTTGACAAAGCAACGGGGGGGATTTAGAGG GCGCGGGGCGTGAGGCGGGACCCCCGCGCCGTGTCCCCCGTGTCCCTCCCTCACCCCGGCCCCCCGCCCG CTGCTTTTTGTTCGGAAGGGGGGGAGAAAGGGGTCCGTAACCAAAGGTGGTCTGCGTCCTTTGGATTCCG ACCCCTCGTCTCCCCCCCTGTCCCCCGCTCTCGGGCTCCTCCCTGCCTCCCTCGCCCCCCCAGAGGGTCG GGGGGCGGCGCACGGCCCACGGGGGTCCCCCGACCGCTTAAGCGGGCCGGGGGTCGGCCCCGTCAAGCGT CCCCGCCCCCGAGCCCACCGCCCGCGACCACCCCCAACCCGCAGCCGGGTGGTCCGGGGAAAAGGGGGGG CCTGAGACCCGGGGGTCGCCCTCTCACCGTGCCGGGGGTCTGCCGCGGCGGCCGCTCGGGGCCGGGGTCC GCCCGGGAGCTCGTGCCGGGCCGGGGTTCCA >gi|109676722|ref|NP_044528.2| ubiquitin E3 ligase ICP0 [Human herpesvirus 2] MEPRPGTSSRADPGPERPPRQTPGTPAAPHAWGMLNDMQWLASSDSEEETEVGISDDDLHRDSTSEAGST DTEMFEAGLMDAATPPARPPAERQGSPTPADAQGSCGGGPVGEEEAEAGGGGDVCAVCTDEIAPPLRCQS FPCLHPFCIPCMKTWIPLRNTCPLCNTPVAYLIVGVTASGSFSTIPIVNDPRTRVEAEAAVRAGTAVDFI WTGNPRTAPRSLSLGGHTVRALSPTPPWPGTDDEDDDLADVDYVPPAPRRAPRRGGGGAGATRGTSQPAA TRPAPPGAPRSSSSGGAPLRAGVGSGSGGGPAVAAVVPRVASLPPAAGGGRAQARRVGEDAAAAEGRTPP ARQPRAAQEPPIVISDSPPPSPRRPAGPGPLSFVSSSSAQVSSGPGGGGLPQSSGRAARPRAAVAPRVRS PPRAAAAPVVSASADAAGPAPPAVPVDAHRAPRSRMTQAQTDTQAQSLGRAGATDARGSGGPGAEGGPGV PRGTNTPGAAPHAAEGAAARPRKRRGSDSGPAASSSASSSAAPRSPLAPQGVGAKRAAPRRAPDSDSGDR GHGPLAPASAGAAPPSASPSSQAAVAAASSSSASSSSASSSSASSSSASSSSASSSSASSSSASSSAGGA GGSVASASGAGERRETSLGPRAAAPRGPRKCARKTRHAEGGPEPGARDPAPGLTRYLPIAGVSSVVALAP YVNKTVTGDCLPVLDMETGHIGAYVVLVDQTGNVADLLRAAAPAWSRRTLLPEHARNCVRPPDYPTPPAS EWNSLWMTPVGNMLFDQGTLVGALDFHGLRSRHPWSREQGAPAPAGDAPAGHGE Virmugen A live-attenuated HSV-2 ICP0 virus provides significant protection against wild-type HSV-2 (MS strain) challenge in mice [Ref1968:Halford et al., 2011]. ICP27 Herpes simplex virus type 1 VO_0011101 75812153 CDD:293457 CDD:283185 10298 ? ICP27 6.82 53658 566 Identical sequence is also seen in starin: BBY-C-1802; laboratory host: Vero cell, human embryonic lung cell >BAE44982.1 ICP27 [Human alphaherpesvirus 1] MATDIDMLIDLGLDLSDSDLDEDPPEPAESRRDDLASDSSGECSSSDEDMEDPHGEDGPEPILDAARPAV RPSRPEDPGVPSTQTPRPTERQGPNDPQPAPHSVWSRLGARRPSCSPEQHGGKVARLQPPPTKAQPARGG RRGRRRGRGRGGPGAADGLSDPRRRAPRTNRNPGGPRPGAGWTDGPGAPHGEAWRGSEQPDPPGGPRTRG VRQAPPPLMTLAIAPPPADPRAPAPERKAPAADTIDATTRLVLRSISERAAVDRISESFGRSAQVMHDPF GGQPFPAANSPWAPVLADQGGPFDAETRRVSWETLVAHGPSLYRTFAGNPRAASTAKAMRDCVLRQENFI EALASADETLAWCKMCIHHNLPLRPQDPIIGTAAAVLDNLATRLRPFLQCYLKARGLCGLDELCSRRRLA DIKDIASFVFVILARLANRVERGVAEIDYATLGVGVGEKMHFYLPGACMAGLIEILDTHRQECSSRVCEL TASHIVAPPYVHGKYFYCNSLF Protective antigen Epitopes from the ICP27 (H1, H2), glycoprotein B (gB) and glycoprotein D (gD) proteins of HSV-1 were attached to either the J TCBL/ICBL or the G TCBL/ICBL. The JH1, JH2, JgB and JgD vaccines elicited DTH responses without antibody but conferred protection upon lethal challenge with HSV [Ref1114:Goel et al., 2005]. ICP27 from Herpes simplex virus type 2 Herpes simplex virus type 2 VO_0011100 124181 CDD:293457 CDD:283185 10315 ? mRNA export factor 7.52 56538.03 697 Immediate-early protein IE63; Infected cell protein 27; VMW63; ICP27 >sp|P28276.1|ICP27_HHV2H RecName: Full=mRNA export factor; AltName: Full=Immediate-early protein IE63; AltName: Full=Infected cell protein 27; Short=ICP27; AltName: Full=VMW63 MATDIDMLIDLGLDLSDSELEEDALERDEEGRRDDPESDSSGECSSSDEDMEDPCGDGGAEAIDAAIPKG PPARPEDAGTPEASTPRPAARRGADDPPPATTGVWSRLGTRRSASPREPHGGKVARIQPPSTKAPHPRGG RRGRRRGRGRYGPGGADSTPKPRRRVSRNAHNQGGRHPASARTDGPGATHGEARRGGEQLDVSGGPRPRG TRQAPPPLMALSLTPPHADGRAPVPERKAPSADTIDPAVRAVLRSISERAAVERISESFGRSALVMQDPF GGMPFPAANSPWAPVLATQAGGFDAETRRVSWETLVAHGPSLYRTFAANPRAASTAKAMRDCVLRQENLI EALASADETLAWCKMCIHHNLPLRPQDPIIGTAAAVLENLATRLRPFLQCYLKARGLCGLDDLCSRRRLS DIKDIASFVLVILARLANRVERGVSEIDYTTVGVGAGETMHFYIPGACMAGLIEILDTHRQECSSRVCEL TASHTIAPLYVHGKYFYCNSLF Protective antigen Particle-mediated DNA vaccination of mice with a DNA plasmid-encoding ICP27 resulted in the induction of ICP27-specific IFN-gamma and TNF-alpha production in Balb/c mice. When the DNA vaccine was supplemented with as little as 50ng of a vector encoding the A and B subunits of the Escherichia coli heat labile enterotoxin (LT), animals were profoundly protected from morbidity and mortality [Ref1113:Haynes et al., 2006]. IgG Mus musculus 16059 AF010213 10090 12 881411 914690 + immunoglobulin heavy chain (V7183 family) Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG) >gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA ACAAGCACAGTGCAAATTTCTGTCACCCTG Vaximmutor Vaximmutor TK Human herpesvirus 1 2703374 9629403 HHV1gp034 X14112 NP_044624 1KIM 10298 46607 47910 - thymidine kinase 8.59 38836.64 376 2.7.1.21 >gi|9629378:46607-47910 Human herpesvirus 1, complete genome TTTTATTCTGTCTTTTTATTGCCGTCATAGCGCGGGTTCCTTCCGGTATTGTCTCCTTCCGTGTTTCAGT TAGCCTCCCCCATCTCCCGGGCAAACGTGCGCGCCAGGTCGCAGATCGTCGGTATGGAGCCTGGGGTGGT GACGTGGGTCTGGACCATCCCGGAGGTAAGTTGCAGCAGGGCGTCCCGGCAGCCGGCGGGCGATTGGTCG TAATCCAGGATAAAGACATGCATGGGACGGAGGCGTTTGGCCAAGACGTCCAAAGCCCAGGCAAACACGT TATACAGGTCGCCGTTGGGGGCCAGCAACTCGGGGGCCCGAAACAGGGTAAATAACGTGTCCCCGATATG GGGTCGTGGGCCCGCGTTGCTCTGGGGCTCGGCACCCTGGGGCGGCACGGCCGCCCCCGAAAGCTGTCCC CAATCCTCCCGCCACGACCCGCCGCCCTGCAGATACCGCACCGTATTGGCAAGCAGCCCATAAACGCGGC GAATCGCGGCCAGCATAGCCAGGTCAAGCCGCTCGCCGGGGCGCTGGCGTTTGGCCAGGCGGTCGATGTG TCTGTCCTCCGGAAGGGCCCCCAACACGATGTTTGTGCCGGGCAAGGTCGGCGGGATGAGGGCCACGAAC GCCAGCACGGCCTGGGGGGTCATGCTGCCCATAAGGTATCGCGCGGCCGGGTAGCACAGGAGGGCGGCGA TGGGATGGCGGTCGAAGATGAGGGTGAGGGCCGGGGGCGGGGCATGTGAGCTCCCAGCCTCCCCCCCGAT ATGAGGAGCCAGAACGGCGTCGGTCACGGCATAAGGCATGCCCATTGTTATCTGGGCGCTTGTCATTACC ACCGCCGCGTCCCCGGCCGATATCTCACCCTGGTCGAGGCGGTGTTGTGTGGTGTAGATGTTCGCGATTG TCTCGGAAGCCCCCAACACCCGCCAGTAAGTCATCGGCTCGGGTACGTAGACGATATCGTCGCGCGAACC CAGGGCCACCAGCAGTTGCGTGGTGGTGGTTTTCCCCATCCCGTGGGGACCGTCTATATAAACCCGCAGT AGCGTGGGCATTTTCTGCTCCAGGCGGACTTCCGTGGCTTTTTGTTGCCGGCGAGGGCGCAACGCCGTAC GTCGGTTGTTATGGCCGCGAGAACGCGCAGCCTGGTCGAACGCAGACGCGTGTTGATGGCAGGGGTACGA AGCCATACGCGCTTCTACAAGGCGCTGGCCGAAGAGGTGCGGGAGTTTCACGCCACCAAGATCTGCGGCA CGCTGTTGACGCTGTTAAGCGGGTCGCTGCAGGGTCGCTCGGTA >gi|9629403|ref|NP_044624.1| thymidine kinase [Human herpesvirus 1] MASYPCHQHASAFDQAARSRGHNNRRTALRPRRQQKATEVRLEQKMPTLLRVYIDGPHGMGKTTTTQLLV ALGSRDDIVYVPEPMTYWRVLGASETIANIYTTQHRLDQGEISAGDAAVVMTSAQITMGMPYAVTDAVLA PHIGGEAGSSHAPPPALTLIFDRHPIAALLCYPAARYLMGSMTPQAVLAFVALIPPTLPGTNIVLGALPE DRHIDRLAKRQRPGERLDLAMLAAIRRVYGLLANTVRYLQGGGSWREDWGQLSGAAVPPQGAEPQSNAGP RPHIGDTLFTLFRAPELLAPNGDLYNVFAWALDVLAKRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQT HVTTPGSIPTICDLARTFAREMGEAN Virmugen A thymidine kinase-deficient (TK) mutant was found to be attenuated in mice. This mutant induced complete protection from challenge with wild type HSV [Ref1982:Field and Wildy, 1978]. UL27 Herpes simplex virus type 2 VO_0011097 1869850 CDD:223014 GOA:P08666 InterPro:IPR000234 UniProtKB/Swiss-Prot:P08666 10310 ? glycoprotein B 8.42 93087.81 972 glycoprotein BALF4; Provisional >CAB06752.1 glycoprotein B [Human alphaherpesvirus 2] MRGGGLICALVVGALVAAVASAAPAAPAAPRASGGVAATVAANGGPASRPPPVPSPATTKARKRKTKKPP KRPEATPPPDANATVAAGHATLRAHLREIKVENADAQFYVCPPPTGATVVQFEQPRRCPTRPEGQNYTEG IAVVFKENIAPYKFKATMYYKDVTVSQVWFGHRYSQFMGIFEDRAPVPFEEVIDKINTKGVCRSTAKYVR NNMETTAFHRDDHETDMELKPAKVATRTSRGWHTTDLKYNPSRVEAFHRYGTTVNCIVEEVDARSVYPYD EFVLATGDFVYMSPFYGYREGSHTEHTSYAADRFKQVDGFYARDLTTKARATSPTTRNLLTTPKFTVAWD WVPKRPAVCTMTKWQEVDEMLRAEYGGSFRFSSDAISTTFTTNLTEYSLSRVDLGDCIGRDAREAIDRMF ARKYNATHIKVGQPQYYLATGGFLIAYQPLLSNTLAELYVREYMREQDRKPRNATPAPLREAPSANASVE RIKTTSSIEFARLQFTYNHIQRHVNDMLGRIAVAWCELQNHELTLWNEARKLNPNAIASATVGRRVSARM LGDVMAVSTCVPVAPDNVIVQNSMRVSSRPGTCYSRPLVSFRYEDQGPLIEGQLGENNELRLTRDALEPC TVGHRRYFIFGGGYVYFEEYAYSHQLSRADVTTVSTFIDLNITMLEDHEFVPLEVYTRHEIKDSGLLDYT EVQRRNQLHDLRFADIDTVIRADANAAMFAGLCAFFEGMGDLGRAVGKVVMGVVGGVVSAVSGVSSFMSN PFGALAVGLLVLAGLVAAFFAFRYVLQLQRNPMKALYPLTTKELKTSDPGGVGGEGEEGAEGGGFDEAKL AEAREMIRYMALVSAMERTEHKARKKGTSALLSSKVTNMVLRKRNKARYSPLHNEDEAGDEDEL Protective antigen The present study evaluated the modulatory functions of salbutamol co-administered with DNA vaccine expressing gB (UL27) of herpes simplex virus (HSV) via intranasal (i.n.) route. The enhanced immune responses caused by co-administration of salbutamol provided effective and rapid responses to HSV mucosal challenge, thereby conferring prolonged survival and reduced inflammation against viral infection [Ref1110:Kim et al., 2009]. UL27 from Herpes simplex virus type 1 Human herpesvirus 1 VO_0011099 2703455 9629408 HHV1gp041 X14112 NP_044629 2GUM 10298 53057 56079 - envelope glycoprotein B 8.23 93545.07 904 glycoprotein BALF4; the Herpesviridae are non-segmented dsDNA viruses with genomes ranging from 120-230kbp; although herpes viruses vary greatly in sequence identity and homology, they all share four common elements: an envelope, a tegument which is composed of viral enzymes, a capsid of 162 capsomers, and a core composed of genomic DNA; BALF4 is a transmembrane glycoprotein found in the lipid envelope of several herpesviruses >NC_001806.1:53057-56079 Human herpesvirus 1, complete genome TTTTATTTACAACAAACCCCCCATCACAGGTCGTCCTCGTCGGCGTCACCGTCTTTGTTGGGAACTTGGG TGTAGTTGGTGTTGCGGCGCTTGCGCATGACCATGTCGGTGACCTTGGCGCTGAGCAGCGCGCTCGTGCC CTTCTTCTTGGCCTTGTGTTCCGTGCGCTCCATGGCAGACACCAGGGCCATGTACCGTATCATCTCCCGG GCCTCGGCTAGCTTGGCCTCGTCAAAGTCGCCGCCCTCCTCGCCCTCCCCGGACGCGTCCGGGTTGGTGG GGTTCTTGAGCTCCTTGGTGGTTAGCGGGTACAGGGCCTTCATGGGGTTGCTCTGCAGCCGCATGACGTA GCGAAAGGCGAAGAAGGCCGCCGCCAGGCCGGCCAGGACCAACAGACCCACGGCCAGCGCCCCAAAGGGG TTGGACATGAAGGAGGACACGCCCGACACGGCCGATACCACGCCGCCCACGATGCCCATCACCACCTTGC CGACCGCGCGCCCCAGGTCGCCCATCCCCTCGAAGAACGCGCCCAGGCCCGCAAACATGGCGGCGTTGGC GTCGGCGTGGATGACCGTGTCGATGTCGGCGAAGCGCAGGTCGTGCAGCTGGTTGCGGCGCTGGACCTCC GTGTAGTCCAGCAGGCCGCTGTCCTTGATCTCGTGGCGGGTGTACACCTCCAGGGGGACAAACTCGTGAT CCTCCAGCATGGTGATGTTGAGGTCGATGAAGGTGCTGACGGTGGTGATGTCGGCGCGGCTCAGCTGGTG GGAGTACGCGTACTCCTCGAAGTACACGTAGCCCCCACCGAAGGTGAAGTAGCGCCGGTGTCCCACGGTG CACGGCTCGATCGCATCGCGCGTCAGCCGCAGCTCGTTGTTCTCCCCCAGCTGCCCCTCGACCAACGGGC CCTGGTCTTCGTACCGAAAGCTGACCAGGGGGCGGCTGTAGCAGGCCCCGGGCCGCGAGCTGATGCGCAT CGAGTTTTGGACGATCACGTTGTCCGCGGCGACCGGCACGCACGTGGAGACGGCCATCACGTCGCCGAGC ATCCGCGCGCTCACCCGCCGGCCCACGGTGGCCGAGGCGATGGCGTTGGGGTTCAGCTTGCGGGCCTCGT TCCACAGGGTCAGCTCGTGATTCTGCAGCTCGCACCACGCGATGGCAACGCGGCCCAACATATCGTTGAC ATGGCGCTGTATGTGGTTGTACGTAAACTGCAGCCTGGCGAACTCGATGGAGGAGGTGGTCTTGATGCGC TCCACGGACGCGTTGGCGCTGGCCCCGGGCGGCGGGGGCGTGGGGTTTGGGGGCTTGCGGCTCTGCTCGC GGAGGTGTTCCCGCACGTACAGCTCCGCGAGCGTGTTGCTGAGAAGGGGCTGGTACGCGATCAGAAAGCC CCCATTGGCCAGGTAGTACTGCGGCTGGCCCACCTTGATGTGCGTCGCGTTGTACCTGCGGGCGAAGATG CGGTCCATGGCGTCGCGGGCGTCCTTGCCGATGCAGTCCCCCAGGTCCACGCGCGAGAGCGGGTACTCGG TCAGGTTGGTGGTGAAGGTGGTGGATATGGCGTCGGAAGAGAATCGGAAGGAGCCGCCGTACTCGGAGCG CAGCATCTCGTCCACCTCCTGCCACTTGGTCATGGTGCAGACCGACGGGCGCTTTGGCACCCAGTCCCAG GCCACGGTGAACTTGGGGGTCGTGAGCAGGTTCCGGGTGGTCGGCGCCGTGGCCCGGGCCTTGGTGGTGA GGTCGCGCGCGTAGAAGCCGTCGACCTGCTTGAAGCGGTCGGCGGCGTAGCTGGTGTGTTCGGTGTGCGA CCCCTCCCGGTAGCCGTAAAACGGGGACATGTACACAAAGTCGCCAGTCGCCAACACAAACTCGTCGTAC GGGTACACCGAGCGCGCGTCCACCTCCTCGACGATGCAGTTTACCGTCGTCCCGTACCGGTGGAACGCCT CCACCCGCGAGGGGTTGTACTTGAGGTCGGTGGTGTGCCAGCCCCGGCTCGTGCGGGTCGCGGCGTTGGC CGGTTTCAGCTCCATGTCGGTCTCGTGGTCGTCCCGGTGAAACGCGGTGGTCTCCAGGTTGTTGCGCACG TACTTGGCCGTGGACCGACAGACCCCCTTGGCGTTGATCTTGTCGATCACCTCCTCGAAGGGGACGGGGG CGCGGTCCTCAAAGATCCCCATAAACTGGGAGTAGCGGTGGCCGAACCACACCTGCGAAACGGTGACGTC TTTGTAGTACATGGTGGCCTTGAACTTGTACGGGGCGATGTTCTCCTTGAAGACCACCGCGATGCCCTCC GTGTAGTTCTGACCCTCGGGCCGGGTCGGGCAGCGGCGCGGCTGCTCGAACTGCACCACCGTGGCGCCCG TGGGGGGTGGGCACACGTAAAAGTTTGCATCGGTGTTCTCCGCCTTGATGTCCCGCAGGTGCTCGCGCAG GGTGGCGTGGCCCGCGGCGACGGTCGCGTTGTCGCCGGCGGGGCGCGGCGGCTTTGGGGGTTTCGGTTTT CTGTTCTTCTTCGGTTTCGGGTCCCCCGTTGGGGGGGCGCCAGGGGCGGGCGGCGCCGGAGTGGCAGGGC CCCCGTTCGCCGCCTGGGTCGCGGCCGCGACCCCAGGCGTGCCGGGGGAACTCGGAGCCGCCGACGCCAC CAGGACCCCCAGCGTCAACCCCAAGAGCGCCCATACGACGAACCACCGGCGCCCCCGCGCGGGGGCGCCC TGGCGCATGGCGGGACTACGGGGGCCCGTCGTGCCCCCCGTCAGGTAGCCTGGGGGCGAGGTGCTGGAGG ACCGAGTAGAGGATCGAGAAAACGTCTCGGTCGTAGACCACGACCGACCGGGGGCCGATACAGCCGTCGG GGGCGCTCTCGACGATGGCCACCAGCGGACAGTCGGAGTCGTACGTGAGATATACGCCGGGCGGGTAACG GTAACGACCTTCGGAGGTCGGGCGGCTGCAGTCCGGGCGGCGCAACTCGAGCTCCCCGCACCGGTAGACC GAGGCAAAGAGTG >NP_044629.1 envelope glycoprotein B [Human herpesvirus 1] MRQGAPARGRRWFVVWALLGLTLGVLVASAAPSSPGTPGVAAATQAANGGPATPAPPAPGAPPTGDPKPK KNRKPKPPKPPRPAGDNATVAAGHATLREHLRDIKAENTDANFYVCPPPTGATVVQFEQPRRCPTRPEGQ NYTEGIAVVFKENIAPYKFKATMYYKDVTVSQVWFGHRYSQFMGIFEDRAPVPFEEVIDKINAKGVCRST AKYVRNNLETTAFHRDDHETDMELKPANAATRTSRGWHTTDLKYNPSRVEAFHRYGTTVNCIVEEVDARS VYPYDEFVLATGDFVYMSPFYGYREGSHTEHTSYAADRFKQVDGFYARDLTTKARATAPTTRNLLTTPKF TVAWDWVPKRPSVCTMTKWQEVDEMLRSEYGGSFRFSSDAISTTFTTNLTEYPLSRVDLGDCIGKDARDA MDRIFARRYNATHIKVGQPQYYLANGGFLIAYQPLLSNTLAELYVREHLREQSRKPPNPTPPPPGASANA SVERIKTTSSIEFARLQFTYNHIQRHVNDMLGRVAIAWCELQNHELTLWNEARKLNPNAIASATVGRRVS ARMLGDVMAVSTCVPVAADNVIVQNSMRISSRPGACYSRPLVSFRYEDQGPLVEGQLGENNELRLTRDAI EPCTVGHRRYFTFGGGYVYFEEYAYSHQLSRADITTVSTFIDLNITMLEDHEFVPLEVYTRHEIKDSGLL DYTEVQRRNQLHDLRFADIDTVIHADANAAMFAGLGAFFEGMGDLGRAVGKVVMGIVGGVVSAVSGVSSF MSNPFGALAVGLLVLAGLAAAFFAFRYVMRLQSNPMKALYPLTTKELKNPTNPDASGEGEEGGDFDEAKL AEAREMIRYMALVSAMERTEHKAKKKGTSALLSAKVTDMVMRKRRNTNYTQVPNKDGDADEDDL Protective antigen Study demonstrated that recombinant Listeria monocytogenes (Lm) expressing the H-2K(b) glycoprotein B (gB, UL27)(498-505) peptide from HSV-1 triggers a robust CD8 T cell response to this Ag resulting in protective immunity to HSV infection in mice [Ref1112:Orr et al., 2007]. UL29 Human herpesvirus 1 2703458 9629410 HHV1gp41.5 X14112 NP_044631 10298 58408 62052 - single-stranded DNA-binding protein 6.48 119914.97 1196 >gi|9629378:58408-62052 Human herpesvirus 1, complete genome ATTTATTTTACACACATTCCCCGCCCCGCCCTAGGTTCCCCCACCCCCCAACCCCTCACAGCATATCCAA CGTCAGGTCTCCCTTTTTGTCGGGGGGCCCCTCCCCAAACGGGTCATCCCCGTGGAACGCCCGTTTGCGG CCGGCAAATGCCGGTCCCGGGGCCCCCGGGCCGCCGAACGGCGTCGCGTTGTCGTCCTCGCAGCCAAAAT CCCCAAAGTTAAACACCTCCCCGGCGTTGCCGAGTTGGCTGACTAGGGCCTCGGCCTCGTGCGCCACCTC CAGGGCCGCGTCCGTCGACCACTCGCCGTTGCCGCGCTCCAGGGCACGCGCGGTCAGCTCCATCATCTCC TCGCTTAGGTACTCGTCCTCCAGGAGCGCCAGCCAGTCCTCGATCTGCAGCTGCTGGGTGCGGGGCCCCA GGCTTTTCACGGTCGCCACGAACACGCTACTGGCGACGGCCGCCCCGCCCTCGGAGATAATGCCCCGGAG CTGCTCGCACAGCGAGCTTTCGTGCGCTCCGCCGCCGAGGCTTGAGGCCGCGCACACAAACCCGGCCCGG GGACAGGCCAGGACGAACTTGCGGGTGCGGTCAAAAATAAGGAGCGGGCACGCGTTTTTGCCGCCCATCA GGCTGGCCCAGTTCCCGGCCTGAAACACACGGTCGTTGCCGGCCATGCCGTAGTACTTGCTGATGCTCAA CCCCAACACGACCATGGGGCGCGCCGCCATGACGGGCCGCAGCAGGTTGCAGCTGGCGAACATGGACGTC CACGCGCCCGGATGCGCGTCCACGGCGTCCATCAGCGCGCGGGCCCCGGCCTCCAGGCCCGCCCCGCCCT GCGCGGACCACGCGGCCGCAGCCTGCACGCTGGGGGGACGGCGGGACCCCGCGATGATGGCCGTAAGGGT GTTGATGAAGTATGTCGAGTGATCGCAGTACCGCAGAATCTGGTTTGCCATGTAGTACATCGCCAGCTCG CTCACGTTGTTGGGGGCCAGGTTAATAAAGTTTATCGCGCCGTAGTCCAGGGAAAACTTTTTAATGAACG CGATGGTCTCGATGTCCTCGCGCGACAGGAGCCGGGCGGGAAGCTGGTTGCGTTGGAGGGCCGTCCAGAA CCACTGCGGGTTCGGCTGGTTGGACCCCGGGGGCTTGCCGTTGGGGAAGATGGCCGCGTGGAACTGCTTC AGCAGAAAGCCCAGCGGTCCGAGGAGGATGTCCACGCGCTTGTCGGGCTTCTGGTAGGCGCTCTGGAGGC TGGCGACCCGCGCCTTGGCGGCCTCGGACGCGTTGGCGCTCGCGCCCGCGAACAACACGCGGCTCTTGAC GCGCAGCTCCTTGGGAAACCCCAGGGTCACGCGGGCAACGTCGCCCTCGAAGCTGCTCTCGGCGGGGGCC GTCTGGCCGGCCGTTAGGCTGGGGGCGCAGATAGCCGCCCCCTCCGAGAGCGCGACCGTCAGCGTTTTGG CCGACAGAAACCCGTTGTTAAACATGTCCATCACGCGCCGCCGCAGCACCGGTTGGAATTGATTGCGAAA GTTGCGCCCCTCGACCGACTGCCCGGCGAACACCCCGTGGCACTGACTCAGGGCCAGGTCCTGGTACACG GCGAGGTTGGATCGCCGCCCGAGAAGCTGAAGCAGGGGGCACGGCCCGCACGCGTACGGGTCCAGCGTCA GGGACATGGCGTGGTTGGCCTCGCCCAGACCGTCGCGAAACTTGAAGTTCCTCCCCTCCACCAGGTTGCG CATCAGCTGCTCCACCTCGCGGTCCACGACCTGCCTGACGTTGTTCACCACCGTATGCAGGGCCTCGCGG TTGGTGATGATGGTCTCCAGCCGCCCCATGGCCGTGGGGACCGCCTGGTCCACGTACTGCAGGGTCTCGA GTTCGGCCATGACGCGCTCGGTCGCCGCGCGGTACGTCTCCTGCATGATGGTCCGGGCGGTCTCGGATCC GTCCGCGCGCTTCAGGGCCGAGAAGGCGGCGTAGTTTCCCAGCACGTCGCAGTCGCTGTACATGCTGTTC ATGGTCCCGAAGACGCCGATGGCTCCGCGGGCGGCGCTGGCGAACTTTGGATGGCGCGCCCGGAGGCGCA TGAGCGTCGTGTGTACGCAGGCGTGGCGCGTGTCGAAGGTGCATAGGTTACAGGGCACGTCGGTCTGGTT GGAGTCCGCGACGTATCGAAACACGTCCATCTCCTGGCGCCCGACGATCACGGCGCCGTCGCAGCGCTCC AGGTAAAACAGCATCTTGGCCAGCAGCGCCGGGGAAAACCCACACAGCATGGCCAGGTGCTCGCCGGCAA ATTCCTGGGTTCCGCCGACGAGGGGCGCGGTGGGCCGACCCTCGAACCCGGGCACCACGTGTCCCTCGCG GTCCACCTGTGGGTTGGCCGCCACGTGGGTCCCGGGCACGAGGAAGAAGCGGTAAAAGGAGGGTTTGCTG TGGTCCTTTGGGTCCGCCGGGCCGGCGTCGTCCACCTCGGTGAGATGGAGGGCCGAGTTGGTGCTAAATA CCATGGCCCCCACGAGTCCCGCGGCGCGCGCCAGGTACGCCCCGACGGCGTTGGCGCGGGCCGCGGCCGT GTCCTGGCCCTCGAACAGCGGCCACGCGGAGATGTCGGTGGGCGGCTCGTCAAAGACGGCCATCGACACG ATAGACTCGAGGGCCAGGGCGGCGTCTCCGGCCATGACGGAGGCCAGGCGCTGTTCGAACCCGCCCGCCG CGCCCTTGCCGCCGCCGTCGCGCCCGCCCCGCGGGGTCTTACCCTGGCTGGCTTCGAAGGCCGTGAACGT AATGTCGGCGGGGAGGGCGGCGCCCTCGTGGTTTTCGTCAAACGCCAGGTGGGCGGCCGCGCGGGCCACG GCGTCCACGTTTCGGCATCGCAGTGCCACGGCGGCGGGTCCCACGACCGCCTCGAACAGGAGGCGGTTGA GGGGGCGGTTAAAAAACGGAAGCGGGTAGGTAAATTTCTCCCCGATCGATCGGTGGTTGGCGTTGAACGG CTCTGCGATGACACGGCTAAAATCCGGCATGAACAGCTGCAACGGGTACACGGGTATGCGGTGCACCTCC GCCCCGCCTATGGTTACCTTGTCCGAGCCTCCCAGGTGCAGAAAGGTGTTGTTGATGCACACGGCCTCCT TGAAGCCCTCGGTAACGACCAGATACAGGAGGGCGCGGTCCGGGTCCAGGCCGAGGCGCTCACACAGCGC CTCCCCCGTCGTCTCGTGTTTGAGGTCGCCGGGCCGGGGGGTGTAGTCCGAAAAGCCAAAATGGCGGCGT GCCCGCTCGCAAAGTCGCGTCAGGTTCGGGGCCTGGGTGCTGGGGTCCAGGTGCCGGCCGCCGTGAAAGA CGTACACGGACGAGCTGTAGTGCGAGGGCGTCAGTTTCAGGGACACCGCGGTACCCCCGAGCCCCGTCGT GCGAGAACCCACGACCACGGCCACGTTGGCCTCAAAGCCGCTCTCCACGGTCAGGCCCACGACCAGGGGC GCCACGGCGACGTCGGAATCGCCGCTGCGTGCCGACAGTAACGCCAGAAGCTCGATGCCTTCGGACGGAC ACGCGCGAGCGTACACGTATCCCAGGGGCCCGGGGGGGACCTTGATGGTGGTTGCCGTCTTGGGCTTTGT CTCCA >gi|9629410|ref|NP_044631.1| single-stranded DNA-binding protein [Human herpesvirus 1] METKPKTATTIKVPPGPLGYVYARACPSEGIELLALLSARSGDSDVAVAPLVVGLTVESGFEANVAVVVG SRTTGLGGTAVSLKLTPSHYSSSVYVFHGGRHLDPSTQAPNLTRLCERARRHFGFSDYTPRPGDLKHETT GEALCERLGLDPDRALLYLVVTEGFKEAVCINNTFLHLGGSDKVTIGGAEVHRIPVYPLQLFMPDFSRVI AEPFNANHRSIGEKFTYPLPFFNRPLNRLLFEAVVGPAAVALRCRNVDAVARAAAHLAFDENHEGAALPA DITFTAFEASQGKTPRGGRDGGGKGAAGGFEQRLASVMAGDAALALESIVSMAVFDEPPTDISAWPLFEG QDTAAARANAVGAYLARAAGLVGAMVFSTNSALHLTEVDDAGPADPKDHSKPSFYRFFLVPGTHVAANPQ VDREGHVVPGFEGRPTAPLVGGTQEFAGEHLAMLCGFSPALLAKMLFYLERCDGAVIVGRQEMDVFRYVA DSNQTDVPCNLCTFDTRHACVHTTLMRLRARHPKFASAARGAIGVFGTMNSMYSDCDVLGNYAAFSALKR ADGSETARTIMQETYRAATERVMAELETLQYVDQAVPTAMGRLETIITNREALHTVVNNVRQVVDREVEQ LMRNLVEGRNFKFRDGLGEANHAMSLTLDPYACGPCPLLQLLGRRSNLAVYQDLALSQCHGVFAGQSVEG RNFRNQFQPVLRRRVMDMFNNGFLSAKTLTVALSEGAAICAPSLTAGQTAPAESSFEGDVARVTLGFPKE LRVKSRVLFAGASANASEAAKARVASLQSAYQKPDKRVDILLGPLGFLLKQFHAAIFPNGKPPGSNQPNP QWFWTALQRNQLPARLLSREDIETIAFIKKFSLDYGAINFINLAPNNVSELAMYYMANQILRYCDHSTYF INTLTAIIAGSRRPPSVQAAAAWSAQGGAGLEAGARALMDAVDAHPGAWTSMFASCNLLRPVMAARPMVV LGLSISKYYGMAGNDRVFQAGNWASLMGGKNACPLLIFDRTRKFVLACPRAGFVCAASSLGGGAHESSLC EQLRGIISEGGAAVASSVFVATVKSLGPRTQQLQIEDWLALLEDEYLSEEMMELTARALERGNGEWSTDA ALEVAHEAEALVSQLGNAGEVFNFGDFGCEDDNATPFGGPGAPGPAFAGRKRAFHGDDPFGEGPPDKKGD LTLDML Virmugen A UL29 mutant is attenuated in mice and induces significant protection from challenge with wild type HSV-1 [Ref1866:Morrison and Knipe, 1994]. UL44 from HSV-1 Human alphaherpesvirus 1 VO_0011103 2703410 820945274 HHV1gp00p31 AJ421498 YP_009137119 10298 96311 98668 + envelope glycoprotein C 7.82 50756.04 511 envelope glycoprotein C; the Herpesviridae are non-segmented dsDNA viruses with genomes ranging from 120-230kbp; although herpes viruses vary greatly in sequence identity and homology, they all share four common elements: an envelope, a tegument which is composed of viral enzymes, a capsid of 162 capsomers, and a core composed of genomic DNA;virion envelope glycoproteins bind to cellular receptors; the nonessential glycoprotein gC interacts with cell surface proteoglycans, whereas the essential glycoprotein gD is involved in stable secondary attachment >NC_001806.2:96311-98668 Human herpesvirus 1 strain 17, complete genome CATGGCCCCGGGGCGGGTGGGCCTTGCCGTGGTCCTGTGGAGCCTGTTGTGGCTCGGGGCGGGGGTGTCC GGGGGCTCGGAAACTGCCTCCACCGGGCCCACGATCACCGCGGGAGCGGTGACGAACGCGAGCGAGGCCC CCACATCGGGGTCCCCCGGGTCAGCCGCCAGCCCGGAGGTCACCCCCACATCGACCCCAAACCCCAACAA TGTCACACAAAACAAAACCACCCCCACCGAGCCGGCCAGCCCCCCAACAACCCCCAAGCCCACCTCCACG CCCAAAAGCCCCCCCACGTCCACCCCCGACCCCAAACCCAAGAACAACACCACCCCCGCCAAGTCGGGCC GCCCCACTAAACCCCCCGGGCCCGTGTGGTGCGACCGCCGCGACCCATTGGCCCGGTACGGCTCGCGGGT GCAGATCCGATGCCGGTTTCGGAATTCCACCCGCATGGAGTTCCGCCTCCAGATATGGCGTTACTCCATG GGTCCGTCCCCCCCAATCGCTCCGGCTCCCGACCTAGAGGAGGTCCTGACGAACATCACCGCCCCACCCG GGGGACTCCTGGTGTACGACAGCGCCCCCAACCTAACGGACCCCCACGTGCTCTGGGCGGAGGGGGCCGG CCCGGGCGCCGACCCTCCGTTGTATTCTGTCACCGGGCCGCTGCCGACCCAGCGGCTGATTATCGGCGAG GTGACGCCCGCGACCCAGGGAATGTATTACTTGGCCTGGGGCCGGATGGACAGCCCGCACGAGTACGGGA CGTGGGTGCGCGTCCGCATGTTCCGCCCCCCGTCTCTGACCCTCCAGCCCCACGCGGTGATGGAGGGTCA GCCGTTCAAGGCGACGTGCACGGCCGCCGCCTACTACCCGCGTAACCCCGTGGAGTTTGTCTGGTTCGAG GACGACCACCAGGTGTTTAACCCGGGCCAGATCGACACGCAGACGCACGAGCACCCCGACGGGTTCACCA CAGTCTCTACCGTGACCTCCGAGGCTGTCGGCGGCCAGGTCCCCCCGCGGACCTTCACCTGCCAGATGAC GTGGCATCGCGACTCCGTGACGTTCTCGCGACGCAATGCCACCGGGCTGGCCCTGGTGCTGCCGCGGCCA ACCATCACCATGGAATTTGGGGTCCGGCATGTGGTCTGCACGGCCGGCTGCGTCCCCGAGGGCGTGACGT TTGCCTGGTTCCTGGGGGACGACCCCTCACCGGCGGCTAAGTCGGCCGTTACGGCCCAGGAGTCGTGCGA CCACCCCGGGCTGGCTACGGTCCGGTCCACCCTGCCCATTTCGTACGACTACAGCGAGTACATCTGTCGG TTGACCGGATATCCGGCCGGGATTCCCGTTCTAGAACACCACGGCAGTCACCAGCCCCCACCCAGGGACC CCACCGAGCGGCAGGTGATCGAGGCGATCGAGTGGGTGGGGATTGGAATCGGGGTTCTCGCGGCGGGGGT CCTGGTCGTAACGGCAATCGTGTACGTCGTCCGCACATCACAGTCGCGGCAGCGTCATCGGCGGTAACGC AAGACCCCCCCGTTACCTTTTTAATATCTATATAGTTTGGTCCCCCCTCTATCCCGCCCACCGCTGGGCG CTATAAAGCCGCCACCCTCTCTTCCCTCAGGTCATCCTTGGTCGATCCCGAACGACACACGGCGTGGAGC AAAACGCCTCCCCCTGAGCCGCTTTCCTACCAACACAACGGCATGCCTCTGCGGGCATCGGAACACGCCT ACCGGCCCCTGGGCCCCGGGACACCCCCCATGCGGGCTCGGCTCCCCGCCGCGGCCTGGGTTGGCGTCGG GACCATCATCGGGGGAGTTGTGATCATTGCCGCGTTGGTCCTCGTGCCCTCGCGGGCCTCGTGGGCACTT TCCCCATGCGACAGCGGATGGCACGAGTTCAACCTCGGGTGCATATCCTGGGATCCGACCCCCATGGAGC ACGAGCAGGCGGTCGGCGGCTGTAGCGCCCCGGCGACCCTGATCCCCCGCGCGGCTGCCAAACAGCTGGC CGCCGTCGCACGCGTCCAGTCGGCAAGATCCTCGGGCTACTGGTGGGTGAGCGGAGACGGCATTCGGGCC TGCCTGCGGCTCGTCGACGGCGTCGGCGGTATTGACCAGTTTTGCGAGGAGCCCGCCCTTCGCATATGCT ACTATCCCCGCAGTCCCGGGGGCTTTGTTCAGTTTGTAACTTCGACCCGCAACGCGCTGGGGCTGCCGTG AGGCGCGTGTACTGCGGTCTGTCTCGTCTCCTCTTCTCCCCTTCCCTCCCCCTCCGCATCCCAGGATCAC ACCGGTCAACGAGGGTTGGGGGGGTCCGGCACGGACCCAAAATAATAA >YP_009137119.1 envelope glycoprotein C [Human alphaherpesvirus 1] MAPGRVGLAVVLWSLLWLGAGVSGGSETASTGPTITAGAVTNASEAPTSGSPGSAASPEVTPTSTPNPNN VTQNKTTPTEPASPPTTPKPTSTPKSPPTSTPDPKPKNNTTPAKSGRPTKPPGPVWCDRRDPLARYGSRV QIRCRFRNSTRMEFRLQIWRYSMGPSPPIAPAPDLEEVLTNITAPPGGLLVYDSAPNLTDPHVLWAEGAG PGADPPLYSVTGPLPTQRLIIGEVTPATQGMYYLAWGRMDSPHEYGTWVRVRMFRPPSLTLQPHAVMEGQ PFKATCTAAAYYPRNPVEFVWFEDDHQVFNPGQIDTQTHEHPDGFTTVSTVTSEAVGGQVPPRTFTCQMT WHRDSVTFSRRNATGLALVLPRPTITMEFGVRHVVCTAGCVPEGVTFAWFLGDDPSPAAKSAVTAQESCD HPGLATVRSTLPISYDYSEYICRLTGYPAGIPVLEHHGSHQPPPRDPTERQVIEAIEWVGIGIGVLAAGV LVVTAIVYVVRTSQSRQRHRR Protective antigen Protection against a lethal intraperitoneal challenge of HSV-1 (5 x 10(4) pfu) with gC (UL44) or gE plasmid vaccination could be demonstrated if the inoculating dose of DNA was 250 microg. All mice immunized with vaccinia recombinants expressing either gC or gE survived HSV-1 challenge [Ref1116:Nass et al., 1998]. US4 Human alphaherpesvirus 2 VO_0011102 1487356 820945216 HHV2p11 JN561323 YP_009137216 10310 137881 140058 + envelope glycoprotein G 8.54 68471.88 699 gD family >NC_001798.2:137881-140058 Human herpesvirus 2 strain HG52, complete genome CATGCACGCCATCGCTCCCAGGTTGCTTCTTCTTTTTGTTCTTTCTGGTCTTCCGGGGACACGCGGCGGG TCGGGTGTCCCCGGACCAATTAATCCCCCCAACAGCGATGTTGTTTTCCCGGGAGGTTCCCCCGTGGCTC AATATTGTTATGCCTATCCCCGGTTGGACGATCCCGGGCCCTTGGGTTCCGCGGACGCCGGGCGGCAAGA CCTGCCCCGGCGCGTCGTCCGTCACGAGCCCCTGGGCCGCTCGTTCCTCACGGGGGGGCTGGTTTTGCTG GCGCCGCCGGTACGCGGATTTGGCGCACCCAACGCAACGTATGCGGCCCGTGTGACGTACTACCGGCTCA CCCGCGCCTGCCGTCAGCCCATCCTCCTTCGGCAGTATGGAGGGTGTCGCGGCGGCGAGCCGCCGTCCCC AAAGACGTGCGGGTCGTACACGTACACGTACCAGGGCGGCGGGCCTCCGACCCGGTACGCTCTCGTAAAT GCTTCCCTGCTGGTGCCGATCTGGGACCGCGCCGCGGAGACATTCGAGTACCAGATCGAACTCGGCGGCG AGCTGCACGTGGGTCTGTTGTGGGTAGAGGTGGGCGGGGAGGGCCCCGGCCCCACCGCCCCCCCACAGGC GGCGCGTGCGGAGGGCGGCCCGTGCGTCCCCCCGGTCCCCGCGGGCCGCCCGTGGCGCTCGGTGCCCCCG GTATGGTATTCCGCCCCCAACCCCGGGTTTCGTGGCCTGCGTTTCCGGGAGCGCTGTCTGCCCCCACAGA CGCCCGCCGCCCCCAGCGACCTACCACGCGTCGCTTTTGCTCCCCAGAGCCTGCTGGTGGGGATTACGGG CCGCACGTTTATTCGGATGGCACGACCCACGGAAGACGTCGGGGTCCTGCCGCCCCATTGGGCCCCCGGG GCCCTAGATGACGGTCCGTACGCCCCCTTCCCACCCCGCCCGCGGTTTCGACGCGCCCTGCGGACAGACC CCGAGGGGGTCGACCCCGACGTTCGGGCCCCCCGAACCGGGCGGCGCCTCATGGCCTTGACCGAGGACAC GTCCTCCGATTCGCCTACGTCCGCTCCGGAGAAGACGCCCCTCCCTGTGTCGGCCACCGCCATGGCACCC TCAGTCGACCCAAGCGCGGAACCGACCGCCCCCGCAACCACTACTCCCCCCGACGAGATGGCCACACAAG CCGCAACGGTCGCCGTTACGCCGGAGGAAACGGCAGTCGCCTCCCCGCCCGCGACTGCATCCGTGGAGTC GTCGCCACTCCCCGCCGCGGCGGCGGCAACGCCCGGGGCCGGGCACACGAACACCAGCAGCGCCTCCGCA GCGAAAACGCCCCCCACCACACCAGCCCCCACGACCCCCCCGCCCACGTCTACCCACGCGACCCCCCGCC CCACGACTCCGGGGCCCCAAACAACCCCTCCCGGACCCGCAACCCCGGGTCCGGTGGGCGCCTCCGCCGC GCCCACGGCCGATTCCCCCCTCACCGCCTCGCCCCCCGCTACCGCGCCGGGGCCCTCGGCCGCCAACGTT TCGGTCGCCGCGACCACCGCCACGCCCGGAACCCGGGGCACCGCCCGTACCCCCCCAACGGACCCAAAGA CGCACCCACACGGACCCGCGGACGCTCCCCCCGGCTCGCCAGCCCCCCCACCCCCCGAACATCGCGGCGG ACCCGAGGAGTTTGAGGGCGCCGGGGACGGCGAACCCCCCGAGGACGACGACAGCGCCACCGGCCTCGCC TTCCGAACTCCGAACCCCAACAAACCACCCCCCGCGCGCCCCGGGCCCATCCGCCCCACGCTCCCGCCAG GAATTCTTGGGCCGCTCGCCCCCAACACGCCTCGCCCCCCCGCCCAAGCTCCCGCTAAGGACATGCCCTC GGGCCCCACACCCCAACACATCCCCCTGTTCTGGTTCCTAACGGCCTCCCCTGCTCTAGATATCCTCTTT ATCATCAGCACCACCATCCACACGGCGGCGTTCGTTTGTCTGGTCGCCTTGGCAGCACAACTTTGGCGCG GCCGGGCGGGGCGCAGGCGATACGCGCACCCGAGCGTGCGTTACGTATGTCTGCCACCCGAGCGGGATTA GGGGGTGGGGGTGGGGGGCGAGAAACGATGAAGGACGGGAAAGGGAACAGCGACCAAATGTCACGATAAG AACAATAA >YP_009137216.1 envelope glycoprotein G [Human alphaherpesvirus 2] MHAIAPRLLLLFVLSGLPGTRGGSGVPGPINPPNSDVVFPGGSPVAQYCYAYPRLDDPGPLGSADAGRQD LPRRVVRHEPLGRSFLTGGLVLLAPPVRGFGAPNATYAARVTYYRLTRACRQPILLRQYGGCRGGEPPSP KTCGSYTYTYQGGGPPTRYALVNASLLVPIWDRAAETFEYQIELGGELHVGLLWVEVGGEGPGPTAPPQA ARAEGGPCVPPVPAGRPWRSVPPVWYSAPNPGFRGLRFRERCLPPQTPAAPSDLPRVAFAPQSLLVGITG RTFIRMARPTEDVGVLPPHWAPGALDDGPYAPFPPRPRFRRALRTDPEGVDPDVRAPRTGRRLMALTEDT SSDSPTSAPEKTPLPVSATAMAPSVDPSAEPTAPATTTPPDEMATQAATVAVTPEETAVASPPATASVES SPLPAAAAATPGAGHTNTSSASAAKTPPTTPAPTTPPPTSTHATPRPTTPGPQTTPPGPATPGPVGASAA PTADSPLTASPPATAPGPSAANVSVAATTATPGTRGTARTPPTDPKTHPHGPADAPPGSPAPPPPEHRGG PEEFEGAGDGEPPEDDDSATGLAFRTPNPNKPPPARPGPIRPTLPPGILGPLAPNTPRPPAQAPAKDMPS GPTPQHIPLFWFLTASPALDILFIISTTIHTAAFVCLVALAAQLWRGRAGRRRYAHPSVRYVCLPPERD Protective antigen In two experiments, mice immunised with phage displaying a single epitope of gG2 (US4) were protected against challenge with a lethal dose of whole HSV-2 [Ref1115:Grabowska et al., 2000]. US5 Human alphaherpesvirus 1 VO_0011098 2703406 820945295 HHV1gp00p10 AY240646 YP_009137140 10298 137598 141051 + mRNA 8.94 8366.08 92 >NC_001806.2:137598-141051 Human herpesvirus 1 strain 17, complete genome TTAAATACATGCCCGGGACCCATGAAGCATGCGCGACTTCCGGGCCTCAGAACCCACCCGAAACGGCCAA CGGACGTCTGAGCCAGGCCTGGCTATCCGGAGAAACAGCACACGACTTGGCGTTCTGTGTGTCGCGATGT CTCTGCGCGCAGTCTGGCATCTGGGGCTTTTGGGAAGCCTCGTGGGGGCTGTTCTTGCCGCCACCCATCG GGGACCTGCGGCCAACACAACGGACCCCTTAACGCACGCCCCAGTGTCCCCTCACCCCAGCCCCCTGGGG GGCTTTGCCGTCCCCCTCGTAGTCGGTGGGCTGTGCGCCGTAGTCCTGGGGGCGGCATGTCTGCTTGAGC TCCTGCGTCGTACGTGCCGCGGGTGGGGGCGTTACCATCCCTACATGGACCCAGTTGTCGTATAATTTCC CCCCCCCCCCCCCTTCTCCGCGTGGGTGATGTCGGGTCCAAACTCCCGACACCACCAGCTGGCATGGTAT AAATCACCGGTGCGCCCCCCAAACCATGTCCGGCAGGGGGATGGGGGGGCGAATGCGGAGGGCACCCAAC AACACCGGGCTAACCAGGAAATCCGTGGCCCCGGCCCCCAATAAAGATCGCGGTAGCCCGGCCGTGTGAC ACTATCGTCCATACCGACCACACCGACGAATCCCCCAAGGGGGAGGGGCCATTTTACGAGGAGGAGGGGT ATAACAAAGTCTGTCTTTAAAAAGCAGGGGTTAGGGAGTTGTTCGGTCATAAGCTTCAGCGCGAACGACC AACTACCCCGATCATCAGTTATCCTTAAGGTCTCTTTTGTGTGGTGCGTTCCGGTATGGGGGGGGCTGCC GCCAGGTTGGGGGCCGTGATTTTGTTTGTCGTCATAGTGGGCCTCCATGGGGTCCGCGGCAAATATGCCT TGGTGGATGCCTCTCTCAAGATGGCCGACCCCAATCGCTTTCGCGGCAAAGACCTTCCGGTCCTGGACCA GCTGACCGACCCTCCGGGGGTCCGGCGCGTGTACCACATCCAGGCGGGCCTACCGGACCCGTTCCAGCCC CCCAGCCTCCCGATCACGGTTTACTACGCCGTGTTGGAGCGCGCCTGCCGCAGCGTGCTCCTAAACGCAC CGTCGGAGGCCCCCCAGATTGTCCGCGGGGCCTCCGAAGACGTCCGGAAACAACCCTACAACCTGACCAT CGCTTGGTTTCGGATGGGAGGCAACTGTGCTATCCCCATCACGGTCATGGAGTACACCGAATGCTCCTAC AACAAGTCTCTGGGGGCCTGTCCCATCCGAACGCAGCCCCGCTGGAACTACTATGACAGCTTCAGCGCCG TCAGCGAGGATAACCTGGGGTTCCTGATGCACGCCCCCGCGTTTGAGACCGCCGGCACGTACCTGCGGCT CGTGAAGATAAACGACTGGACGGAGATTACACAGTTTATCCTGGAGCACCGAGCCAAGGGCTCCTGTAAG TACGCCCTCCCGCTGCGCATCCCCCCGTCAGCCTGCCTCTCCCCCCAGGCCTACCAGCAGGGGGTGACGG TGGACAGCATCGGGATGCTGCCCCGCTTCATCCCCGAGAACCAGCGCACCGTCGCCGTATACAGCTTGAA GATCGCCGGGTGGCACGGGCCCAAGGCCCCATACACGAGCACCCTGCTGCCCCCGGAGCTGTCCGAGACC CCCAACGCCACGCAGCCAGAACTCGCCCCGGAAGACCCCGAGGATTCGGCCCTCTTGGAGGACCCCGTGG GGACGGTGGCGCCGCAAATCCCACCAAACTGGCACATACCGTCGATCCAGGACGCCGCGACGCCTTACCA TCCCCCGGCCACCCCGAACAACATGGGCCTGATCGCCGGCGCGGTGGGCGGCAGTCTCCTGGCAGCCCTG GTCATTTGCGGAATTGTGTACTGGATGCGCCGCCACACTCAAAAAGCCCCAAAGCGCATACGCCTCCCCC ACATCCGGGAAGACGACCAGCCGTCCTCGCACCAGCCCTTGTTTTACTAGATACCCCCCCTTAATGGGTG CGGGGGGGTCAGGTCTGCGGGGTTGGGATGGGACCTTAACTCCATATAAAGCGAGTCTGGAAGGGGGGAA AGGTGGACAGTCGATAAGTCGGTAGCGGGGGACGCGCACCTGTTCCGCCTGTCGCACCCACAGCTTTTTT TGCGAACCGTCCCGTTCCGGGATGCCGTGCCGCCCGTTGCAGGGCCTGGTGCTCGTGGGCCTCTGGGTCT GTGCCACCAGCCTGGTTGTCCGTGGCCCCACGGTCAGTCTGGTATCAAACTCATTTGTGGACGCCGGGGC CTTGGGGCCCGACGGCGTAGTGGAGGAAGACCTGCTTATTCTCGGGGAGCTTCGCTTTGTGGGGGACCAG GTCCCCCACACCACCTACTACGATGGGGGCGTAGAGCTGTGGCACTACCCCATGGGACACAAATGCCCAC GGGTCGTGCATGTCGTCACGGTGACCGCGTGCCCACGTCGCCCCGCCGTGGCATTCGCCCTGTGTCGCGC GACCGACAGCACTCACAGCCCCGCATATCCCACCCTGGAGCTCAATCTGGCCCAACAGCCGCTTTTGCGG GTCCAGAGGGCAACGCGGGACTATGCCGGGGTGTACGTGTTACGCGTATGGGTCGGTGACGCGCCAAACG CCAGCCTGTTTGTCCTGGGGATGGCCATAGCCGCCGAAGGGACTCTGGCGTACAACGGCTCGGCCTATGG CTCCTGCGACCCGAAACTGCTTCCGTCTTCGGCCCCGCGTCTGGCCCCGGCGAGCGTATACCAACCCGCC CCTAACCAGGCCTCCACCCCCTCGACCACCACCTCCACCCCCTCGACCACCATCCCCGCTCCCTCGACCA CCATCCCCGCTCCCCAAGCATCGACCACGCCCTTCCCCACGGGAGATCCAAAACCACAACCTCCCGGGGT CAACCACGAACCCCCATCTAATGCCACGCGAGCGACCCGCGACTCGCGATACGCGCTAACGGTGACCCAG ATAATCCAGATAGCCATCCCCGCGTCCATCATAGCCCTGGTGTTTCTGGGGAGCTGTATTTGCTTTATAC ACAGATGTCAACGCCGCTACCGACGCTCCCGTCGCCCGATTTACAGCCCCCAGATGCCCACGGGCATCTC ATGCGCGGTGAACGAAGCGGCCATGGCCCGCCTCGGAGCCGAGCTCAAATCGCATCCGAGCACCCCCCCC AAATCCCGGCGCCGGTCGTCACGCACGCCAATGCCCTCCCTGACGGCCATCGCCGAAGAGTCGGAGCCCG CTGGGGCGGCTGGGCTTCCGACGCCCCCCGTGGACCCCACGACACCCACCCCAACGCCTCCCCTGTTGGT ATAGGTCCACGGCCACTGGCCGGGAGCACCACATAACCGACCGCAGTCCCTGAGTTGGGAATAAACCGGT ATTATTTACCTATATCCGTGTATG >YP_009137140.1 envelope glycoprotein J [Human alphaherpesvirus 1] MSLRAVWHLGLLGSLVGAVLAATHRGPAANTTDPLTHAPVSPHPSPLGGFAVPLVVGGLCAVVLGAACLL ELLRRTCRGWGRYHPYMDPVVV Protective antigen BALB/c mice receiving a glycoprotein D1 (gD1, US5) DNA vaccine alone were 80% protected against a subsequent HSV-1 challenge. Results also indicate that the administration of NLX as an adjuvant improved protective immunity against HSV-1 [Ref1111:Jamali et al., 2009]. US7 Human herpesvirus 1 strain McKrae 388525000 CDD:223033 CDD:279953 10298 ? gI 9.08 40934 462 type: 1 >AFK50416.1 gI [Human alphaherpesvirus 1] MQGLVLVGLWVCATSLVVRGPTVSLVSNSFVDAGALGPDGVVEEDLLILGELRFVGDQVPHTTYYDGVVE LWHYPMGHKCPRVVHVVTVTACPRRPAVAFALCRATDNTHSPAYPTLELNLAQQPLLRVRRATRDYAGVY VLRVWVVDAPNASLFVLGMAIAAEGTLAYNGSAHGSCDPKLLPYSAPRLAPASVYQPAPNPASTPSTTTS TPSTTTSTPSTTTSTPSTTTSTPSTTTSTPSTTTSTPSTTIPAPQASTTPFPTGDPKPQPHGVNHEPPSN ATRATRDSRYALTVTQIIQIAIPASIIALVFLGSCICFIHRCQRRYRRSRRPIYNPQIPTGISCAVNEAA MARLGAELKSHPSTPPKSRRRSSRTPMPSLTAIAEESEPAGAAGLPTPPVDPTTSTPTPPLLV Protective antigen US8 Human alphaherpesvirus 1 VO_0011104 2703448 820945298 HHV1gp00p07 AJ626470 YP_009137143 10298 141142 143696 + mRNA 6.08 54133.1 550 >NC_001806.2:141142-143696 Human herpesvirus 1 strain 17, complete genome GCATTTAAGGCGTTGTTGTGTTGACTTTGCCTCTTCTGGCGGGTTGGTGCGGTGCTGTTTGTTGGGCTCC CATTTTACCCGAAGATCGGCTGCTATCCCCGGGACATGGATCGCGGGGCGGTGGTGGGGTTTCTTCTCGG TGTTTGTGTTGTATCGTGCTTGGCGGGAACGCCCAAAACGTCCTGGAGACGGGTGAGTGTCGGCGAGGAC GTTTCGTTGCTTCCAGCTCCGGGGCCTACGGGGCGCGGCCCGACCCAGAAACTACTATGGGCCGTGGAAC CCCTGGATGGGTGCGGCCCCTTACACCCGTCGTGGGTCTCGCTGATGCCCCCCAAGCAGGTGCCCGAGAC GGTCGTGGATGCGGCGTGCATGCGCGCTCCGGTCCCGCTGGCGATGGCGTACGCCCCCCCGGCCCCATCT GCGACCGGGGGTCTACGAACGGACTTCGTGTGGCAGGAGCGCGCGGCCGTGGTTAACCGGAGTCTGGTTA TTCACGGGGTCCGAGAGACGGACAGCGGCCTGTATACCCTGTCCGTGGGCGACATAAAGGACCCGGCTCG CCAAGTGGCCTCGGTGGTCCTGGTGGTGCAACCGGCCCCAGTTCCGACCCCACCCCCGACCCCAGCCGAT TACGACGAGGATGACAATGACGAGGGCGAGGACGAAAGTCTCGCCGGCACTCCCGCCAGCGGGACCCCCC GGCTCCCGCCTCCCCCCGCCCCCCCGAGGTCTTGGCCCAGCGCCCCCGAAGTCTCACATGTGCGTGGGGT GACCGTGCGTATGGAGACTCCGGAAGCTATCCTGTTTTCCCCCGGGGAGACGTTCAGCACGAACGTCTCC ATCCATGCCATCGCCCACGACGACCAGACCTACTCCATGGACGTCGTCTGGTTGAGGTTCGACGTGCCGA CCTCGTGTGCCGAGATGCGAATATACGAATCGTGTCTGTATCACCCGCAGCTCCCAGAATGTCTGTCCCC GGCCGACGCGCCGTGCGCCGCGAGTACGTGGACGTCTCGCCTGGCCGTCCGCAGCTACGCGGGGTGTTCC AGAACAAACCCCCCACCGCGCTGTTCGGCCGAGGCTCACATGGAGCCCGTCCCGGGGCTGGCGTGGCAGG CGGCCTCCGTCAATCTGGAGTTCCGGGACGCGTCCCCACAACACTCCGGCCTGTATCTGTGTGTGGTGTA CGTCAACGACCATATTCACGCCTGGGGCCACATTACCATCAGCACCGCGGCGCAGTACCGGAACGCGGTG GTGGAACAGCCCCTCCCACAGCGCGGCGCGGATTTGGCCGAGCCCACCCACCCGCACGTCGGGGCCCCTC CCCACGCGCCCCCAACCCACGGCGCCCTGCGGTTAGGGGCGGTGATGGGGGCCGCCCTGCTGCTGTCTGC ACTGGGGTTGTCGGTGTGGGCGTGTATGACCTGTTGGCGCAGGCGTGCCTGGCGGGCGGTTAAAAGCAGG GCCTCGGGTAAGGGGCCCACGTACATTCGCGTGGCCGACAGCGAGCTGTACGCGGACTGGAGCTCGGACA GCGAGGGAGAACGCGACCAGGTCCCGTGGCTGGCCCCCCCGGAGAGACCCGACTCTCCCTCCACCAATGG ATCCGGCTTTGAGATCTTATCACCAACGGCTCCGTCTGTATACCCCCGTAGCGATGGGCATCAATCTCGC CGCCAGCTCACAACCTTTGGATCCGGAAGGCCCGATCGCCGTTACTCCCAGGCCTCCGATTCGTCCGTCT TCTGGTAAGGCGCCCCATCCCGAGGCCCCACGTCGGTCGCCGAACTGGGCGACCGCCGGCGAGGTGGACG TCGGAGACGAGCTAATCGCGATTTCCGACGAACGCGGACCCCCCCGACATGACCGCCCGCCCCTCGCCAC GTCGACCGCGCCCTCGCCACACCCGCGACCCCCGGGCTACACGGCCGTTGTCTCCCCGATGGCCCTCCAG GCTGTCGACGCCCCCTCCCTGTTTGTCGCCTGGCTGGCCGCTCGGTGGCTCCGGGGGGCTTCCGGCCTGG GGGCCGTCCTGTGTGGGATTGCGTGGTATGTGACGTCAATTGCCCGAGGCGCATAAAGGGCCGGTGGTCC GCCTAGCCGCAGCAAATTAAAAATCGTGAGTCACAGCGACCGCAACTTCCCACCCGGAGCTTTCTTCCGG CCTCGATGACGTCCCGGCTCTCCGATCCCAACTCCTCAGCGCGATCCGACATGTCCGTGCCGCTTTATCC CACGGCCTCGCCAGTTTCGGTCGAAGCCTACTACTCGGAAAGCGAAGACGAGGCGGCCAACGACTTCCTC GTACGCATGGGCCGCCAACAGTCGGTATTAAGGCGTCGACGCAGACGCACCCGCTGCGTCGGCATGGTGA TCGCCTGTCTCCTCGTGGCCGTTCTGTCGGGCGGATTTGGGGCGCTCCTGATGTGGCTGCTCCGCTAAAA GACCGCATCGACACGCGCGTCCTTCTTGTCGTCTCTCTTCCCCCCCATCACCCCGCAATTTGCACCCAGC CTTTAACTACATTAAATTGGGTTCGATTGGCAATG >YP_009137143.1 envelope glycoprotein E [Human alphaherpesvirus 1] MDRGAVVGFLLGVCVVSCLAGTPKTSWRRVSVGEDVSLLPAPGPTGRGPTQKLLWAVEPLDGCGPLHPSW VSLMPPKQVPETVVDAACMRAPVPLAMAYAPPAPSATGGLRTDFVWQERAAVVNRSLVIHGVRETDSGLY TLSVGDIKDPARQVASVVLVVQPAPVPTPPPTPADYDEDDNDEGEDESLAGTPASGTPRLPPPPAPPRSW PSAPEVSHVRGVTVRMETPEAILFSPGETFSTNVSIHAIAHDDQTYSMDVVWLRFDVPTSCAEMRIYESC LYHPQLPECLSPADAPCAASTWTSRLAVRSYAGCSRTNPPPRCSAEAHMEPVPGLAWQAASVNLEFRDAS PQHSGLYLCVVYVNDHIHAWGHITISTAAQYRNAVVEQPLPQRGADLAEPTHPHVGAPPHAPPTHGALRL GAVMGAALLLSALGLSVWACMTCWRRRAWRAVKSRASGKGPTYIRVADSELYADWSSDSEGERDQVPWLA PPERPDSPSTNGSGFEILSPTAPSVYPRSDGHQSRRQLTTFGSGRPDRRYSQASDSSVFW Protective antigen Protection against a lethal intraperitoneal challenge of HSV-1 (5 x 10(4) pfu) with gC or gE (US8) plasmid vaccination could be demonstrated if the inoculating dose of DNA was 250 microg. All mice immunized with vaccinia recombinants expressing either gC or gE survived HSV-1 challenge [Ref1116:Nass et al., 1998]. Virmugen An HSV-1 gE (Us8) deletion strain, NS-gEnull, was used as a live attenuated vaccine. After HSV-1 challenge, latent virus was recovered by DRG explant cocultures from <10% of vaccinated mice compared with 100% of mock-vaccinated mice [Ref1794:Brittle et al., 2008]. 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