Porcine respiratory and reproductive syndrome virus 28344 Porcine Reproductive and Respiratory Syndrome (PRRS), Blue-Ear Pig Disease Infected pigs develop a strong and rapid humoral response but these initial antibodies do not confer protection and can even be harmful by mediating an antibody-dependent enhancement of disease. In contrast, development of neutralising antibodies (NAs) is delayed and generation of cell-mediated immune responses, such as PRRSV-specific interferon (IFN)-gamma secreting cells, is initially erratic. In spite of this, induction of strong and rapid NAs and IFN-gamma responses seem to be required for effective vaccination. PRRSV strongly modulates the host's immune responses. The virus inhibits key cytokines, such as IFN-alpha, and may induce regulatory cytokines, such as interleukin (IL)-10 (Mateu and Diaz, 2008). Pigs The PRRSV is an enveloped, single-stranded positive-sense RNA virus, approximately 50–65 nm in diameter that is classified in the order Nidovirales, family Arteriviridae, genus Arterivirus along with equine arteritis virus, lactate dehydrogenase-elevating virus of mice, and simian hemorrhagic fever virus. Properties of these viruses include the ability to induce prolonged viremia, persistent infections, and replication in macrophages. Being an enveloped virus, PRRSV survivability outside of the host is affected by temperature, pH and exposure to detergents. It is known that PRRSV can survive for extended intervals (>4 months) at temperatures ranging from −70 to −20 °C; however, viability decreases with increasing temperature. Regarding genetic diversity, there are two major prototypes of PRRSV, the European isolate (Lelystad virus, LV) and the North American isolate (VR-2332). Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease of swine, estimated to cost the swine industry in USA approximately US$ 560 million per year. Clinical outbreaks of PRRS were first reported in the late 1980's in the USA; however, the etiology of the disease remained unknown. Clinical signs included severe reproductive failure, post-weaning pneumonia, growth reduction, decreased performance, and increased mortality. Similar clinical outbreaks were reported in Germany in 1990 and were widespread throughout Europe by 1991. In 1991, the etiologic agent, porcine reproductive and respiratory syndrome virus (PRRSV) was identified by investigators in The Netherlands and USA. Today, PRRSV is endemic in the global swine population; however, several countries, including Sweden, Switzerland, New Zealand, and Australia claim to be free of the disease (Cho and Dee, 2006). 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 Porcine Reproductive & Respiratory Syndrome Reproductive & Respiratory Form, Modified Live Virus Vaccine (USDA: 19T1.20) Boehringer Ingelheim Vetmedica, Inc., Intervet Inc. VO_0001799 Live, attenuated vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome Reproductive & Respiratory Form, Modified Live Virus Vaccine (USDA: 19T1.21) Boehringer Ingelheim Vetmedica, Inc. VO_0001800 Live, attenuated vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome Reproductive Form, Killed Virus Vaccine (USDA: 19S5.20) Intervet Inc. VO_0001801 Inactivated or "killed" vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome Reproductive Form, Modified Live Virus Vaccine (USDA: 19Q1.20) Intervet Inc. VO_0001802 Live, attenuated vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome Respiratory Form, Modified Live Virus Vaccine (USDA: 19S1.20) Wyeth, Boehringer Ingelheim Vetmedica, Inc. VO_0001803 Live, attenuated vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome Respiratory Form, Modified Live Virus Vaccine (USDA: 19S1.21) Boehringer Ingelheim Vetmedica, Inc. VO_0001804 Live, attenuated vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome Respiratory Form, Modified Live Virus Vaccine-Erysipelothrix Rhusiopathiae-Haemophilus Parasuis Bacterin (USDA: 49V9.20) Boehringer Ingelheim Vetmedica, Inc. VO_0004214 Live, attenuated vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome Respiratory Form, Modified Live Virus Vaccine-Haemophilus Parasuis Bacterin (USDA: 49Q9.20) Boehringer Ingelheim Vetmedica, Inc. VO_0004217 Live, attenuated vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome-Circovirus Reproductive & Respiratory Form, Type 2, Modifed Live Virus,Killed Baculovirus Vector Vaccine-Mycoplasma Hyopneumoniae Bacterin (USDA: 49K9.R0) Boehringer Ingelheim Vetmedica, Inc. VO_0002317 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA Porcine Reproductive & Respiratory Syndrome-Parvovirus Reproductive Form, Modified Live & Killed Virus Vaccine-Erysipelothrix Rhusiopathiae-Leptospira Canicola-Grippotyphosa-Hardjo-Icterohaemorrhagiae-Pomona Bacterin (USDA: 4P19.20) Boehringer Ingelheim Vetmedica, Inc. VO_0002324 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA Porcine respiratory and reproductive syndrome virus GP5 protein mutant vaccine HuN4-F112 VO_0002982 Live, attenuated vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) Gene mutation This GP5 protein mutant is from Porcine reproductive and respiratory syndrome virus (Tian et al., 2009). A GP5 protein mutant is attenuated in piglets (Tian et al., 2009). A GP5 protein mutant induces protection in piglets from challenge with wild type HP-PRRSV (Tian et al., 2009). PRRSV DNA vaccine GST-ORF5 encoding GP5 VO_0004325 DNA vaccine Research pET21a [Ref2161:Pirzadeh and Dea, 1998] Intramuscular injection (i.m.) Freund's complete or incomplete adjuvant (Pirzadeh and Dea, 1998) Intramuscular injection (i.m.) DNA vaccine construction Vector pET21a expressed the major envelope glycoprotein (GP5) of porcine reproductive and respiratory syndrome virus (PRRSV) (Pirzadeh and Dea, 1998). VO_0000286 Following a massive intratracheal challenge with the virulent IAF-Klop strain of PRRSV, DNA-vaccinated pigs were protected from generalized viraemia and the development of typical macroscopic lung lesions that were observed in unvaccinated, virus-challenged controls, as well as in pigs that were immunized with E. coli-expressed GST-ORF5 recombinant fusion protein (Pirzadeh and Dea, 1998). PRRSV DNA vaccine pCA-U-optiGP5 VO_0004506 DNA vaccine Research pCAGGS [Ref2439:Hou et al., 2008] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pCAGGS expressed the U-optiGP5 fusion gene was generated by linking optiGP5 downstream of ubiquitin. The Kozak sequence, GCCACC, served as the upstream start codon for all three fragments (Hou et al., 2008). DNA vaccine construction This vaccine expressed a sequence encoding pig ubiquitin that had its Gly76 changed to Ala76 (Hou et al., 2008). VO_0000286 Four of six pigs in the pCA-U-optiGP5 group were devoid of visible pathological changes that were present in other vaccinated and control animals after challenge (Hou et al., 2008). PRRSV DNA vaccine pCI-ORF5/ORF6 VO_0004510 DNA vaccine Research pCI-neo [Ref2441:Jiang et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pCl-neo expressed GP5 (encoded by ORF5) and M (encoded by ORF6) (Jiang et al., 2006). VO_0000286 All immunized piglets developed neutralizing antibodies at 10 weeks after primary immunization, whereas there was no detectable neutralizing antibodies in piglets immunized with pCI-ORF5. Neutralizing antibodies are considered to be important in protection against PRRSV (Jiang et al., 2006). PRRSV DNA vaccine pIRESorf5/IFNγ VO_0004507 DNA vaccine Research pIRES1neo (CLONTECH) [Ref2440:Xue et al., 2004] Intramuscular injection (i.m.) IFNG (Xue et al., 2004) Intramuscular injection (i.m.) DNA vaccine construction Vector pIRES1neo expressed GP5, encoded by ORF5, the major envelope protein of the virus harboring neutralizing epitopes (Xue et al., 2004). VO_0000286 After immunization and viral challenge, two of three pigs immunized with pIRESorf5/IFNgamma were protected from lung lesions that were present in other vaccinated and control animals (Cho and Dee, 2006). PRRSV DNA vaccine pIRESorf5/IL-2 VO_0004508 DNA vaccine Research pIRES1neo (CLONTECH) [Ref2440:Xue et al., 2004] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pIRES1neo expressed GP5, encoded by ORF5, the major envelope protein of the virus harboring neutralizing epitopes (Xue et al., 2004). VO_0000286 After immunization and viral challenge, one of three pigs immunized with pIRESorf5/IL-2 was protected from lung lesions that were present in other vaccinated and control animals (Xue et al., 2004). PRRSV DNA vaccine pIRESorf7/IL-2 VO_0004509 DNA vaccine Research pIRES1neo [Ref2440:Xue et al., 2004] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pIRES1neo expressed N, encoded by ORF7, which forms the nucleocapsid protein of the virus, and it is likely to contain virus-specific T cell epitopes (Xue et al., 2004). VO_0000286 After immunization and viral challenge, one of three pigs immunized with pIRESorf7/IL-2 was protected from lung lesions that were present in other vaccinated and control animals (Xue et al., 2004). GP5 Porcine reproductive and respiratory syndrome virus YA1 71152867 CDD:109986 28344 ? major envelope glycoprotein 8.09 20738.03 298 Arterivirus GL envelope glycoprotein; pfam00951 >AAZ29507.1 major envelope glycoprotein [Porcine reproductive and respiratory syndrome virus] MLGKCLTTGCCSRLLSLWCIVPFCFAVLVNANSNSSSHFQLIYNLTLCELNGTDWLANKFDWPVETFVIF PVLTHIVSYGALTTSHFLDTVGLVTVSTAGFYHGRYVLSSIYAVCALAALNCFVIRLAKNCISWRYSCTR YTNFLLDPKGRLYRWRSPVIVEEGGKVEVEGHLIDLKRVVLDGSVATPLTRDSAEQWGRL Protective antigen GP5 protein Porcine reproductive and respiratory syndrome virus strain HUN4 149389584 CDD:109986 28344 ? GP5 200 genotype: North American >gi|149389584|gb|ABR26253.1| GP5 [Porcine reproductive and respiratory syndrome virus] MLGKCLTACCCSRLLFLWCIVPFYLAVLVNASNNNSSHIQLIYNLTLCELNGTDWLAQKFDWAVETFVIF PVLTHIVSYGALTTSHFLDTVGLATVSTAGYYHGRYVLSSIYAVCALAALICFVIRLAKNCMSWRYSCTR YTNFLLDTKGRLYRWRSPVIVEKGGKVEVEGHLIDLKRVVLDGSAATPLTRVSAEQWGRL Virmugen A mutation in the GP5 protein attenuates HP-PRRSV in piglets. This mutant (HuN4-F112) induces protection against challenge with wild type HP-PRRSV [Ref1868:Tian et al., 2009]. ORF5 Porcine reproductive and respiratory syndrome virus 14250961 CDD:109986 28344 ? GP5 envelope protein 8.7 20800.27 291 genotype: North America >AAK44216.1 GP5 envelope protein [Porcine reproductive and respiratory syndrome virus] MLGKCLTTGCCSRLLSLWCIVPFCFAVLVNANSNSSSHFQLIYNLTLCELNGTDWLANKFDWAVETFVIF PVLTHIVSYGALTTSHFLDTVGLVTVSTAGFYHGRYVLSSIYAVCALAALICFVIRLAKNCMSWRYSCTR YTNFLLDTKGRLYRWRSPVIVEKGGKVEVEGHLIDLKRVVLDGSVATPLTRVSAEQWGRL Protective antigen ORF7 Porcine reproductive and respiratory syndrome virus CH-1a 14250964 CDD:110480 28344 ? nucleocapsid protein 10.87 13394.22 213 genotype: North America >AAC15449.2 nucleocapsid protein [Porcine reproductive and respiratory syndrome virus] MPNNNGKQRKKKKGNGQPVNQLCQMLGKIIAQQNQSRGKGPGKKNKKKSPEKPHFPLATEDDVRHHFTPS ERQLCLSSIQTAFNQGAGTCTLSDSGRISYTVEFSLPTHHTVRLIRVTASPSA Protective antigen ubiquitin Sus scrofa 164707 164708 AAA31133.1 CDD:294102 CDD:176398 CDD:214563 9823 ? ubiquitin copy 1 7.82 27768.96 319 Ubiquitin-like proteins; cl00155 >gi|164707|gb|M18159.1|PIGUBP Pig poly-ubiquitin mRNA, 3' end GAAGATGGGCGCACCCTGTCTGACTACAACATCCAGAAGGAGTCCACCCTGCACCTGGTCCTCCGCCTCA GAGGTGGGATGCAGATCTTCGTGAAGACCTTGACTGGTAAGACCATCACCCTGGAAGTGGAGCCCAGCGA CACCATCGAGAATGTCAAGGCGAAGATCCAAGACAAGGAAGGCATCCCCCCAGACCAGCAGAGGCTGATC TTTGCCGGGAAGCAGCTGGAAGATGGGCGCACCCTGTCTGACTACAACATCCAGAAGGAGTCCACCCTGC ACCTGGTCCTCCGCCTCAGAGGTGGGATGCAGATCTTCGTGAAGACCTTGACTGGTAAGACCATCACCCT GGAAGTGGAGCCCAGCGACACCATCGAGAATGTCAAGGCGAAGATCCAAGACAAGGAAGGCATCCCCCCA GACCAGCAGAGGCTGATCTTTGCCGGGAAGCAGCTGGAAGATGGGCGCACCCTGTCTGACTACAACATCC AGAAGGAGTCCACCCTGCACCTGGTCCTCCGCCTCAGAGGTGGGATGCAGATCTTCGTGAAGACCTTGAC TGGTAAGACCATCACCCTGGAAGTGGAGCCCAGCGACACCATCGAGAACGTCAAGGCGAAGATCCAGGAC AAGGAAGGCATCCCCCCAGACCAGCAGAGGCTGATCTTTGCCGGGAAGCAGCTGGAAGATGGGCGCACCC TGTCTGACTACAACATCCAGAAGGAGTCCACCCTGCACTTGGTCCTGCGCTTGAGGGGAGGTTTCTAAGT TCTCCCTTTTAAGCTTTCAACAAATTTCATTGCACTTTTCTTTCAATAAAGTTGTTGCATTC >AAA31133.1 poly-ubiquitin precursor, partial [Sus scrofa] EDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLI FAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPP DQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQD KEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGF Protective antigen An et al., 2018 journal An CH, Nazki S, Park SC, Jeong YJ, Lee JH, Park SJ, Khatun A, Kim WI, Park YI, Jeong JC, Kim CY 2018 247 4 973-985 Planta Cho and Dee, 2006 journal Cho JG, Dee SA 2006 66 3 655-662 Theriogenology Hou et al., 2008 journal Hou YH, Chen J, Tong GZ, Tian ZJ, Zhou YJ, Li GX, Li X, Peng JM, An TQ, Yang HC 2008 26 11 1438-1449 Vaccine Jiang et al., 2006 journal Jiang Y, Xiao S, Fang L, Yu X, Song Y, Niu C, Chen H 2006 24 15 2869-2879 Vaccine Mateu and Diaz, 2008 journal Mateu E, Diaz I 2008 177 3 345-351 Veterinary journal (London, England : 1997) Mokhtar et al., 2017 journal Mokhtar H, Biffar L, Somavarapu S, Frossard JP, McGowan S, Pedrera M, Strong R, Edwards JC, Garcia-Durán M, Rodriguez MJ, Stewart GR, Steinbach F, Graham SP 2017 209 66-74 Veterinary microbiology Pirzadeh and Dea, 1998 journal Pirzadeh B, Dea S 1998 79 ( Pt 5) 989-999 The Journal of general virology Subramaniam et al., 2017 journal Subramaniam S, Piñeyro P, Derscheid RJ, Madson DM, Magstadt DR, Meng XJ 2017 190 18-25 Veterinary immunology and immunopathology Tian et al., 2009 journal Tian ZJ, An TQ, Zhou YJ, Peng JM, Hu SP, Wei TC, Jiang YF, Xiao Y, Tong GZ 2009 138 1-2 34-40 Veterinary microbiology Xue et al., 2004 journal Xue Q, Zhao YG, Zhou YJ, Qiu HJ, Wang YF, Wu DL, Tian ZJ, Tong GZ 2004 102 3 291-298 Veterinary immunology and immunopathology