Varicella-zoster virus 10335 VZV share much genome homology with the herpes simplex viruses (HSV). The capsid is surrounded by a number of loosely associated proteins known collectively as the tegument. Many of these tegument proteins play critical roles in initiating the process of virus reproduction in the infected cell. The tegument is in turn covered by a lipid envelope studded with glycoproteins that are displayed on the exterior of the virion (Wiki: Varicella zoster). chickenpox / shingles Varicella zoster virus (VZV) is one of eight herpes viruses known to infect humans (and other vertebrates). Varicella zoster virus is known by many names, including: chickenpox virus, varicella virus, zoster virus, and human herpes virus type 3 (HHV-3). It commonly causes chicken-pox in children and both shingles and postherpetic neuralgia in adults. Primary VZV infection results in chickenpox (varicella). After clinical symptoms of chickenpox have resolved, VZV remains dormant in the nervous system of the infected person (virus latency). In about 10-20% of cases, VZV reactivates later in life producing a disease known as herpes zoster or shingles. Serious complications of shingles include postherpetic neuralgia, zoster multiplex, myelitis, herpes ophthalmicus, or zoster sine herpete (Wiki: Varicella zoster). 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 licensed Varicella (chickenpox) and herpes zoster (shingles) human vaccine Generic Unknown VO_0000669 Live, attenuated vaccine Licensed A generic representation of vaccines used to prevent chickenpox and shingles in humans, most commonly formulated as live, attenuated virus preparations. These vaccines contain weakened forms of the varicella-zoster virus to stimulate protective immunity without causing disease. Priorix-Tetra Priorix-Tetra GlaxoSmithKline VO_0010735 Live vaccine Licensed Subcutaneous injection Canada Products: Live virus. Other components: Lactose. Store at at 2 to 8°C. Do not freeze Subcutaneous injection ProQuad Measles, Mumps, Rubella and Varicella Virus Vaccine Live ProQuad Merck & Co, Inc. VO_0000091 Live, attenuated vaccine Licensed Intramuscular injection (i.m.) USA (License #0002) ProQuad is a sterile lyophilized preparation of (1) the components of M-M-R*II (Measles, Mumps and Rubella Virus Vaccine Live): Measles Virus Vaccine Live, a more attenuated line of measles virus, derived from Enders' attenuated Edmonston strain and propagated in chick embryo cell culture; Mumps Virus Vaccine Live, the Jeryl Lynn™ (B level) strain of mumps virus propagated in chick embryo cell culture; Rubella Virus Vaccine Live, the Wistar RA 27/3 strain of live attenuated rubella virus propagated in WI-38 human diploid lung fibroblasts; and (2) Varicella Virus Vaccine Live (Oka/Merck) refrigerator-stable formulation, the Oka/Merck strain of varicella-zoster virus propagated in MRC-5 cells (FDA: ProQuad). maintained at a temperature of 2° to 8°C (36° to 46°F) or colder. propagated in MRC-5 cells (FDA: ProQuad). Intramuscular injection (i.m.) According to clinical trials, there were high levels of antibodies in 97.5% of those vaccinated after a single dose of Proquad (FDA: ProQuad). Side effects of vaccination include: injection site reactions, fever, irritability and diarrhea. Varicella Subunit Vaccine encoding gI and gE glycoproteins VO_0004153 Subunit vaccine Research Intramuscular injection (i.m.) Freund's adjuvant (Kimura et al., 1998). Intramuscular injection (i.m.) Recombinant varicella-zoster virus (VZV) glycoproteins E (gE) and I (gI) (Kimura et al., 1998). Recombinant protein preparation Recombinant protein preparation Hartley Female Hartley guinea pigs (5 weeks old) were immunized with either a mixture of purified re- combinant gE and gI (25 μg each) or the recombinant gE-gI complex (50 μg). Purified protein solutions (0.25 mL) were injected intramuscularly with 0.25 mL of complete Freund's adjuvant at the first injection followed with incomplete Freund's adjuvant at the second and third injections at 2-week intervals. Control animals received 0.25 mL of PBS and an equal amount of adjuvant (Kimura et al., 1998). In the gE-gI-immunized group, VZV was isolated from only 1 of 4 animals, and this animal had the lowest CMI and the lowest titer of anti-gE and anti-gI antibodies in the vitreous body. In contrast, VZV was isolated from 3 of 4 animals in the adjuvant-alone group (Kimura et al., 1998). To determine whether immunization with gE and gI can enhance the clearance of VZV in vivo, both immunized and control (adjuvant- alone) guinea pigs were challenged with VZV. Animals were inoculated intravitreally with 200 pfu of cell-associated VZV 4 weeks after the final immunization. At 4 h after inoculation, 4 animals from each group were sacrificed, and their eyes were harvested to test for infectious VZV (Kimura et al., 1998). Varilrix Varilrix GlaxoSmithKline VO_0010746 Live vaccine Licensed Subcutaneous injection Canada Products: Live virus. Other components: Human albumin, Lactose. Store at 2-8°C (36-46°F). Subcutaneous injection Varivax Varicella Virus Vaccine Live Varivax Merck & Co., Inc. VO_0000119 Live, attenuated vaccine Licensed Intradermal injection (i.d.) USA (License #0002) Indication: For active immunization of persons 12 months of age and older. DO NOT FREEZE, store at 2 to 8°C or colder (36 to 46°F or colder). The OkaIMerck strain of live, attenuated varicella vlrus was initially obtained from a child with wild-type varicella, then introduced into human embryonic lung cell'cultures, adapted to and propagated in embryonic guinea pig cell cultures and finally propagated in human diploid cell cultures (WI-38). This live, attenuated varicella vaccine is a lyophllized preparation containing sucrose, phosphate, glutamate, processed gelatin, and urea as stabilizers. The product contains no preservative (FDA: Varivax). Intradermal injection (i.d.) OkaIMerck strain of live, attenuated varicella vlrus. Clinical trials with several formulations of VARIVAX containing the attenuated virus ranging from 1000 to 50,000 PFU per dose, have demonstrated that VARIVAX induces detectable immune responses and is generally well tolerated in healthy individuals ranging from 12 months to 55 years of age. VARIVAX was also found to induce cell-mediated immune responses in vaccinees (FDA: Varivax). The majority of subjects who received the vaccine and were exposed to wild-type virus were either completely protected from chickenpox or developed a milder form of the disease. Clinical studies have demonstrated continued protection up to 10 years after vaccination. Also, a boost in antibody levels has been observed in vaccinees following exposure to wild-type varicella as well as following a second dose of the vaccine (FDA: Varivax). Side effects of vaccination were mostly injection site redness and pain. Varivax III Varivax III Merck Frosst VO_0010747 Live vaccine Licensed Subcutaneous injection Canada Products: Live virus. Other components: Bovine serum, Glutamate, Residual protein from cell culture, Sucrose, Urea. Subcutaneous injection Zostavax Zoster Vaccine, Live, (Oka/Merck) Zostavax Merck & Co., Inc. VO_0000124 Live, attenuated vaccine Licensed USA (License #0002) Indication: Prevention of herpes zoster (shingles) in individuals 60 years of age and older when administered as a single-dose (FDA: Zostavax). ZOSTAVAX SHOULD BE stored FROZEN at an average temperature of -15°C (+5°F) or colder. ZOSTAVAX is a lyophilized preparation of live, attenuated varicella-zoster virus (Oka/Merck) to be reconstituted with sterile diluent to give a single dose suspension with a minimum of 19,400 PFU (plaque forming units) when stored at room temperature for up to 30 minutes (FDA: Zostavax). live, attenuated varicella-zoster virus (Oka/Merck) According to clinical studies, ZOSTAVAX significantly reduced the risk of developing zoster when compared with placebo. Vaccine efficacy for the prevention of herpes-zoster (HZ) was highest for those subjects 60-69 years of age and declined with increasing age (FDA: Zostavax). The most common side effects reported included headache and injection site reactions (FDA: Zostavax). ORF67 Human alphaherpesvirus 3 VO_0011247 1487689 9625941 HHV3_gp68 AF206304 NP_040189 10335 114495 115591 + envelope glycoprotein I 8.22 36387.83 354 envelope glycoprotein I; 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; envelope glycoprotein E and glycoprotein I form a heterodimer that play important roles in virus cell-to-cell spread >NC_001348.1:114495-115591 Human herpesvirus 3, complete genome GATGTTTTTAATCCAATGTTTGATATCGGCCGTTATATTTTACATACAAGTGACCAACGCTTTGATCTTC AAGGGCGACCACGTGAGCTTGCAAGTTAACAGCAGTCTCACGTCTATCCTTATTCCCATGCAAAATGATA ATTATACAGAGATAAAAGGACAGCTTGTCTTTATTGGAGAGCAACTACCTACCGGGACAAACTATAGCGG AACACTGGAACTGTTATACGCGGATACGGTGGCGTTTTGTTTCCGGTCAGTACAAGTAATAAGATACGAC GGATGTCCCCGGATTAGAACGAGCGCTTTTATTTCGTGTAGGTACAAACATTCGTGGCATTATGGTAACT CAACGGATCGGATATCAACAGAGCCGGATGCTGGTGTAATGTTGAAAATTACCAAACCGGGAATAAATGA TGCTGGTGTGTATGTACTTCTTGTTCGGTTAGACCATAGCAGATCCACCGATGGTTTCATTCTTGGTGTA AATGTATATACAGCGGGCTCGCATCACAACATTCACGGGGTTATCTACACTTCTCCGTCTCTACAGAATG GATATTCTACAAGAGCCCTTTTTCAACAAGCTCGTTTGTGTGATTTACCCGCGACACCCAAAGGGTCCGG TACCTCCCTGTTTCAACATATGCTTGATCTTCGTGCCGGTAAATCGTTAGAGGATAACCCTTGGTTACAT GAGGACGTTGTTACGACAGAAACTAAGTCCGTTGTTAAGGAGGGGATAGAAAATCACGTATATCCAACGG ATATGTCCACGTTACCCGAAAAGTCCCTTAATGATCCTCCAGAAAATCTACTTATAATTATTCCTATAGT AGCGTCTGTCATGATCCTCACCGCCATGGTTATTGTTATTGTAATAAGCGTTAAGCGACGTAGAATTAAA AAACATCCAATTTATCGCCCAAATACAAAAACAAGAAGGGGCATACAAAATGCGACACCAGAATCCGATG TGATGTTGGAGGCCGCCATTGCACAACTAGCAACGATTCGCGAAGAATCCCCCCCACATTCCGTTGTAAA CCCGTTTGTTAAATAGAACTAATTATCCCGGATTTTATATTAAATAA >NP_040189.1 envelope glycoprotein I [Human alphaherpesvirus 3] MFLIQCLISAVIFYIQVTNALIFKGDHVSLQVNSSLTSILIPMQNDNYTEIKGQLVFIGEQLPTGTNYSG TLELLYADTVAFCFRSVQVIRYDGCPRIRTSAFISCRYKHSWHYGNSTDRISTEPDAGVMLKITKPGIND AGVYVLLVRLDHSRSTDGFILGVNVYTAGSHHNIHGVIYTSPSLQNGYSTRALFQQARLCDLPATPKGSG TSLFQHMLDLRAGKSLEDNPWLHEDVVTTETKSVVKEGIENHVYPTDMSTLPEKSLNDPPENLLIIIPIV ASVMILTAMVIVIVISVKRRRIKKHPIYRPNTKTRRGIQNATPESDVMLEAAIAQLATIREESPPHSVVN PFVK Protective antigen Monoclonal antibodies to gI neutralize VZV in vitro in a complement- dependent manner [Ref1272:Keller et al., 1986]. Guinea pigs immunized with recombinant varicella-zoster virus (VZV) glycoproteins E (gE) and I (gI) developed antigen-specific antibodies in the sera, vitreous, and conjunctival washes. Sera from immunized animals neutralized both cell-free and cell-associated VZV, and peripheral blood lymphocytes proliferated in vitro in response to recombinant gE and gI and to antigens from VZV-infected cells. Immunized guinea pigs were inoculated intravitreally with VZV, which induces chronic uveitis. VZV DNA was more rapidly cleared and infectious VZV was isolated less frequently from the retinas of animals immunized with gE and gI compared with that in controls receiving adjuvant alone [Ref1251:Kimura et al., 1998]. ORF68 Human alphaherpesvirus 3 VO_0011246 1487709 9625942 HHV3_gp69 AH010255 NP_040190 10335 115807 117720 + envelope glycoprotein E 5.24 64995.36 623 envelope glycoprotein E; 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; envelope glycoprotein E and glycoprotein I form a heterodimer that play important roles in virus cell-to-cell spread >NC_001348.1:115807-117720 Human herpesvirus 3, complete genome TATGGGGACAGTTAATAAACCTGTGGTGGGGGTATTGATGGGGTTCGGAATTATCACGGGAACGTTGCGT ATAACGAATCCGGTCAGAGCATCCGTCTTGCGATACGATGATTTTCACACCGATGAAGACAAACTGGATA CAAACTCCGTATATGAGCCTTACTACCATTCAGATCATGCGGAGTCTTCATGGGTAAATCGGGGAGAGTC TTCGCGAAAAGCGTACGATCATAACTCACCTTATATATGGCCACGTAATGATTATGATGGATTTTTAGAG AACGCACACGAACACCATGGGGTGTATAATCAGGGCCGTGGTATCGATAGCGGGGAACGGTTAATGCAAC CCACACAAATGTCTGCACAGGAGGATCTTGGGGACGATACGGGCATCCACGTTATCCCTACGTTAAACGG CGATGACAGACATAAAATTGTAAATGTGGACCAACGTCAATACGGTGACGTGTTTAAAGGAGATCTTAAT CCAAAACCCCAAGGCCAAAGACTCATTGAGGTGTCAGTGGAAGAAAATCACCCGTTTACTTTACGCGCAC CGATTCAGCGGATTTATGGAGTCCGGTACACCGAGACTTGGAGCTTTTTGCCGTCATTAACCTGTACGGG AGACGCAGCGCCCGCCATCCAGCATATATGTTTAAAACATACAACATGCTTTCAAGACGTGGTGGTGGAT GTGGATTGCGCGGAAAATACTAAAGAGGATCAGTTGGCCGAAATCAGTTACCGTTTTCAAGGTAAGAAGG AAGCGGACCAACCGTGGATTGTTGTAAACACGAGCACACTGTTTGATGAACTCGAATTAGACCCCCCCGA GATTGAACCGGGTGTCTTGAAAGTACTTCGGACAGAAAAACAATACTTGGGTGTGTACATTTGGAACATG CGCGGCTCCGATGGTACGTCTACCTACGCCACGTTTTTGGTCACCTGGAAAGGGGATGAAAAAACAAGAA ACCCTACGCCCGCAGTAACTCCTCAACCAAGAGGGGCTGAGTTTCATATGTGGAATTACCACTCGCATGT ATTTTCAGTTGGTGATACGTTTAGCTTGGCAATGCATCTTCAGTATAAGATACATGAAGCGCCATTTGAT TTGCTGTTAGAGTGGTTGTATGTCCCCATCGATCCTACATGTCAACCAATGCGGTTATATTCTACGTGTT TGTATCATCCCAACGCACCCCAATGCCTCTCTCATATGAATTCCGGTTGTACATTTACCTCGCCACATTT AGCCCAGCGTGTTGCAAGCACAGTGTATCAAAATTGTGAACATGCAGATAACTACACCGCATATTGTCTG GGAATATCTCATATGGAGCCTAGCTTTGGTCTAATCTTACACGACGGGGGCACCACGTTAAAGTTTGTAG ATACACCCGAGAGTTTGTCGGGATTATACGTTTTTGTGGTGTATTTTAACGGGCATGTTGAAGCCGTAGC ATACACTGTTGTATCCACAGTAGATCATTTTGTAAACGCAATTGAAGAGCGTGGATTTCCGCCAACGGCC GGTCAGCCACCGGCGACTACTAAACCCAAGGAAATTACCCCCGTAAACCCCGGAACGTCACCACTTCTAC GATATGCCGCATGGACCGGAGGGCTTGCAGCAGTAGTACTTTTATGTCTCGTAATATTTTTAATCTGTAC GGCTAAACGAATGAGGGTTAAAGCCTATAGGGTAGACAAGTCCCCGTATAACCAAAGCATGTATTACGCT GGCCTTCCAGTGGACGATTTCGAGGACTCGGAATCTACGGATACGGAAGAAGAGTTTGGTAACGCGATTG GAGGGAGTCACGGGGGTTCGAGTTACACGGTGTATATAGATAAGACCCGGTGATCACCGAACCGGGGCAA CGCCGAGCGTGTAAATTTAAATAA >NP_040190.1 envelope glycoprotein E [Human alphaherpesvirus 3] MGTVNKPVVGVLMGFGIITGTLRITNPVRASVLRYDDFHTDEDKLDTNSVYEPYYHSDHAESSWVNRGES SRKAYDHNSPYIWPRNDYDGFLENAHEHHGVYNQGRGIDSGERLMQPTQMSAQEDLGDDTGIHVIPTLNG DDRHKIVNVDQRQYGDVFKGDLNPKPQGQRLIEVSVEENHPFTLRAPIQRIYGVRYTETWSFLPSLTCTG DAAPAIQHICLKHTTCFQDVVVDVDCAENTKEDQLAEISYRFQGKKEADQPWIVVNTSTLFDELELDPPE IEPGVLKVLRTEKQYLGVYIWNMRGSDGTSTYATFLVTWKGDEKTRNPTPAVTPQPRGAEFHMWNYHSHV FSVGDTFSLAMHLQYKIHEAPFDLLLEWLYVPIDPTCQPMRLYSTCLYHPNAPQCLSHMNSGCTFTSPHL AQRVASTVYQNCEHADNYTAYCLGISHMEPSFGLILHDGGTTLKFVDTPESLSGLYVFVVYFNGHVEAVA YTVVSTVDHFVNAIEERGFPPTAGQPPATTKPKEITPVNPGTSPLLRYAAWTGGLAAVVLLCLVIFLICT AKRMRVKAYRVDKSPYNQSMYYAGLPVDDFEDSESTDTEEEFGNAIGGSHGGSSYTVYIDKTR Protective antigen Monoclonal antibodies to gE neutralize VZV in vitro in a complement- dependent manner [Ref1271:Wu and Forghani, 1997]. Guinea pigs immunized with recombinant varicella-zoster virus (VZV) glycoproteins E (gE) and I (gI) developed antigen-specific antibodies in the sera, vitreous, and conjunctival washes. Sera from immunized animals neutralized both cell-free and cell-associated VZV, and peripheral blood lymphocytes proliferated in vitro in response to recombinant gE and gI and to antigens from VZV-infected cells. Immunized guinea pigs were inoculated intravitreally with VZV, which induces chronic uveitis. VZV DNA was more rapidly cleared and infectious VZV was isolated less frequently from the retinas of animals immunized with gE and gI compared with that in controls receiving adjuvant alone [Ref1251:Kimura et al., 1998]. FDA: ProQuad website http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094051.htm FDA: Varivax website http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094073.htm FDA: Zostavax website http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094075.htm GSK: Varilrix website http://www.gsk.ca/english/docs-pdf/varilrix_PM_20070110.pdf Keller et al., 1986 journal Keller PM, Lonergan K, Neff BJ, Morton DA, Ellis RW 1986 14 2 177-188 Journal of virological methods Kimura et al., 1998 journal Kimura H, Wang Y, Pesnicak L, Cohen JI, Hooks JJ, Straus SE, Williams RK 1998 178 2 310-317 The Journal of infectious diseases Wiki: Varicella zoster website http://en.wikipedia.org/wiki/Varicella_zoster Wu and Forghani, 1997 journal Wu L, Forghani B 1997 142 2 349-362 Archives of virology