Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory
Abstract
:1. Introduction
2. Continuing Threat of Smallpox and Other Zoonotic Orthopoxviruses
2.1. Remaining VARV Stocks
2.2. Recreation of Orthopoxviruses by Synthetic Biology
2.3. Emergence and Re-Emergence of Orthopoxviruses
3. Vaccine Development against Smallpox and Other Orthopoxviruses
4. Immune Response against Virus Infection: Basis for an Efficient Vaccine
Immune Response against Vaccinia Virus Infection
5. Vaccine Engineering by Targeting Vaccinia Virus Proteins That Inhibit the Immune Response
5.1. Host Range Proteins
5.2. Secreted Proteins
5.2.1. Protein C21: Vaccinia Complement Control Protein—VCP
5.2.2. Protein A41: A Secreted Chemokine-Binding Protein
5.2.3. vCCI: A Secreted CC Chemokine-Binding Protein
5.2.4. C12: A Soluble IL-18-Binding Protein
5.2.5. Protein B15: A Soluble IL-1β Receptor
5.2.6. Proteins B8 and B18: IFN-Binding Proteins
5.2.7. Other VACV Secreted Proteins
5.3. Intracellular Immunomodulators
5.3.1. VACV Bcl-2-Like Proteins
Protein B14: An NF-κB Inhibitor
Protein N1: An Inhibitor of Apoptosis and NF-κB
Protein K7: An NF-κB and IRF3 Inhibitor
Protein A52: An NF-κB Inhibitor
Protein A46: An Inhibitor of IRF3, NF-κB and MAPK Pathways
Protein C6: And IRF3 and JAK-STAT Signalling Inhibitor
Protein N2: An IRF3 Inhibitor
Protein F1: An Inhibitor of Apoptosis and the Inflammasome
5.3.2. Proteins C4 and C16
5.3.3. De-Capping Enzymes D9 and D10
5.3.4. Protein 169: An Inhibitor of Translation
5.3.5. Protein A35
5.3.6. Protein A44: A 3β-Hydroxysteroid Dehydrogenase
5.3.7. Other Intracellular Virulence Factors or Immunomodulators
5.4. Expression of Cellular Immunomodulators from Vaccinia Virus
6. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
- WHO. The Global Eradication of Smallpox. Final Report of the Global Commission for the Certification of Smallpox Eradication; World Health Organization: Geneva, Switzerland, 1980; Volume 4. [Google Scholar]
- Yamanouchi, K. Scientific background to the global eradication of rinderpest. Vet. Immunol. Immunopathol. 2012, 148, 12–15. [Google Scholar] [CrossRef] [PubMed]
- Patel, M.K.; Gacic-Dobo, M.; Strebel, P.M.; Dabbagh, A.; Mulders, M.N.; Okwo-Bele, J.M.; Dumolard, L.; Rota, P.A.; Kretsinger, K.; Goodson, J.L. Progress toward regional measles elimination—Worldwide, 2000–2015. MMWR Morb. Mortal. Wkly. Rep. 2016, 65, 1228–1233. [Google Scholar] [CrossRef] [PubMed]
- Kowalzik, F.; Faber, J.; Knuf, M. MMR and MMRV vaccines. Vaccine 2017. [Google Scholar] [CrossRef] [PubMed]
- Hall, V.; Banerjee, E.; Kenyon, C.; Strain, A.; Griffith, J.; Como-Sabetti, K.; Heath, J.; Bahta, L.; Martin, K.; McMahon, M.; et al. Measles Outbreak—Minnesota April-May 2017. MMWR Morb. Mortal. Wkly. Rep. 2017, 66, 713–717. [Google Scholar] [CrossRef] [PubMed]
- England, P.H. Measles outbreaks across Europe and the start of the summer festival season. Health Prot. Rep. 2017, 11, 1–3. [Google Scholar]
- Vivancos, R.; Keenan, A.; Farmer, S.; Atkinson, J.; Coffey, E.; Dardamissis, E.; Dillon, J.; Drew, R.J.; Fallon, M.; Huyton, R.; et al. An ongoing large outbreak of measles in Merseyside, England, January to June 2012. Euro Surveill 2012, 17, 905–913. [Google Scholar] [CrossRef]
- Wales, N. Measles Outbreak: Data. Available online: http://www.wales.nhs.uk/sitesplus/888/page/66389#a (accessed on 13 November 2017).
- WHO. Measles Outbreaks across Europe Threaten Progress towards Elimination. Available online: http://www.euro.who.int/en/media-centre/sections/press-releases/2017/measles-outbreaks-across-europe-threaten-progress-towards-elimination (accessed on 13 November 2017).
- Leite, R.D.; Berezin, E.N. Measles in Latin America: Current situation. J. Pediatr. Infect. Dis. Soc. 2015, 4, 179–181. [Google Scholar] [CrossRef] [PubMed]
- Fenner, F.; Henderson, D.A.; Arita, I.; Jezek, Z.; Ladnyi, I.D. Smallpox and Its Eradication; World Health Organization: Geneva, Switzerland, 1988. [Google Scholar]
- Moss, B. Poxviridae. In Fields Virology, 6th ed.; Knipe, D.M., Howley, P.M., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2013; Volume 2, pp. 2129–2159. [Google Scholar]
- Jacobs, B.L.; Langland, J.O.; Kibler, K.V.; Denzler, K.L.; White, S.D.; Holechek, S.A.; Wong, S.; Huynh, T.; Baskin, C.R. Vaccinia virus vaccines: Past, present and future. Antivir. Res. 2009, 84, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Jenner, E. An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease Discovered in Some of the Western Counties of England Particularly Gloucestershire, and Known by the Name of Cow Pox; Sampson Low: London, UK, 1798. [Google Scholar]
- Jenner, E. The Origin of the Vaccine Inoculation; D.N. Shury: London, UK, 1801. [Google Scholar]
- Tuells, J. Vaccinology: The name, the concept, the adjectives. Vaccine 2012, 30, 5491–5495. [Google Scholar] [CrossRef] [PubMed]
- Damaso, C.R. Revisiting Jenner’s mysteries, the role of the Beaugency lymph in the evolutionary path of ancient smallpox vaccines. Lancet Infect. Dis. 2018, 18, e55–e63. [Google Scholar] [CrossRef]
- Fenner, F.; Wittek, R.; Dumbell, K.R. The Orthopoxviruses; Academic Press Ltd.: London, UK, 1989; Chapter 4. [Google Scholar]
- Domi, A.; Moss, B. Cloning the vaccinia virus genome as a bacterial artificial chromosome in Escherichia coli and recovery of infectious virus in mammalian cells. Proc. Natl. Acad. Sci. USA 2002, 99, 12415–12420. [Google Scholar] [CrossRef] [PubMed]
- Noyce, R.S.; Lederman, S.; Evans, D.H. Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments. PLoS ONE 2018, 13, e0188453. [Google Scholar] [CrossRef] [PubMed]
- Massung, R.F.; Esposito, J.J.; Liu, L.I.; Qi, J.; Utterback, T.R.; Knight, J.C.; Aubin, L.; Yuran, T.E.; Parsons, J.M.; Loparev, V.N.; et al. Potential virulence determinants in terminal regions of variola smallpox virus genome. Nature 1993, 366, 748–751. [Google Scholar] [CrossRef] [PubMed]
- Esposito, J.J.; Sammons, S.A.; Frace, A.M.; Osborne, J.D.; Olsen-Rasmussen, M.; Zhang, M.; Govil, D.; Damon, I.K.; Kline, R.; Laker, M.; et al. Genome sequence diversity and clues to the evolution of variola (smallpox) virus. Science 2006, 313, 807–812. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. WHO Recommendations Concerning the Distribution, Handling and Synthesis of Variola Virus DNA; World Health Organization: Geneva, Switzerland, 2016; pp. 1–4. [Google Scholar]
- Smith, G.L.; McFadden, G. Smallpox: Anything to declare? Nat. Rev. Immunol. 2002, 2, 521–527. [Google Scholar] [CrossRef] [PubMed]
- McFadden, G. Killing a killer: What next for smallpox? PLoS Pathog. 2010, 6, e1000727. [Google Scholar] [CrossRef] [PubMed]
- National Intitutes of Health (NIH). Report of the Blue Ribbon Pannel to Review the 2014 Smallpox (Variola) Virus Incident in the NIH Campus; NIH: Bethesda, MD, USA, 2017; p. 50.
- Duggan, A.T.; Perdomo, M.F.; Piombino-Mascali, D.; Marciniak, S.; Poinar, D.; Emery, M.V.; Buchmann, J.P.; Duchene, S.; Jankauskas, R.; Humphreys, M.; et al. 17th century variola virus reveals the recent history of smallpox. Curr. Biol. 2016, 26, 3407–3412. [Google Scholar] [CrossRef] [PubMed]
- Henderson, D.A. Smallpox virus destruction and the implications of a new vaccine. Biosecur. Bioterror. 2011, 9, 163–168. [Google Scholar] [CrossRef] [PubMed]
- Weinstein, R.S. Should remaining stockpiles of smallpox virus (variola) be destroyed? Emerg. Infect. Dis. 2011, 17, 681–683. [Google Scholar] [CrossRef] [PubMed]
- Shchelkunov, S.N. An increasing danger of zoonotic orthopoxvirus infections. PLoS Pathog. 2013, 9, e1003756. [Google Scholar] [CrossRef] [PubMed]
- Jezek, Z.; Fenner, F. Human Monkeypox; Karger: Basel, Switzerland, 1988. [Google Scholar]
- Centers for Disease Control and Prevention. Update: Multistate outbreak of monkeypox—Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR Morb. Mortal. Wkly. Rep. 2003, 52, 642–646. [Google Scholar]
- NCDC. Monkeypox outbreak in Nigeria. Situat. Rep. 2017, 2, 1–2. [Google Scholar]
- Rimoin, A.W.; Mulembakani, P.M.; Johnston, S.C.; Lloyd Smith, J.O.; Kisalu, N.K.; Kinkela, T.L.; Blumberg, S.; Thomassen, H.A.; Pike, B.L.; Fair, J.N.; et al. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc. Natl. Acad. Sci. USA 2010, 107, 16262–16267. [Google Scholar] [CrossRef] [PubMed]
- Campe, H.; Zimmermann, P.; Glos, K.; Bayer, M.; Bergemann, H.; Dreweck, C.; Graf, P.; Weber, B.K.; Meyer, H.; Buttner, M.; et al. Cowpox virus transmission from pet rats to humans, Germany. Emerg. Infect. Dis. 2009, 15, 777–780. [Google Scholar] [CrossRef] [PubMed]
- Ninove, L.; Domart, Y.; Vervel, C.; Voinot, C.; Salez, N.; Raoult, D.; Meyer, H.; Capek, I.; Zandotti, C.; Charrel, R.N. Cowpox virus transmission from pet rats to humans, France. Emerg. Infect. Dis. 2009, 15, 781–784. [Google Scholar] [CrossRef] [PubMed]
- Vogel, S.; Sardy, M.; Glos, K.; Korting, H.C.; Ruzicka, T.; Wollenberg, A. The Munich outbreak of cutaneous cowpox infection: Transmission by infected pet rats. Acta Derm. Venereol. 2012, 92, 126–131. [Google Scholar] [PubMed]
- Wolfs, T.F.; Wagenaar, J.A.; Niesters, H.G.; Osterhaus, A.D. Rat-to-human transmission of cowpox infection. Emerg. Infect. Dis. 2002, 8, 1495–1496. [Google Scholar] [CrossRef] [PubMed]
- Schoniger, S.; Chan, D.L.; Hollinshead, M.; Humm, K.; Smith, G.L.; Beard, P.M. Cowpox virus pneumonia in a domestic cat in Great Britain. Vet. Rec. 2007, 160, 522–523. [Google Scholar] [CrossRef] [PubMed]
- McInerney, J.; Papasouliotis, K.; Simpson, K.; English, K.; Cook, S.; Milne, E.; Gunn-Moore, D.A. Pulmonary cowpox in cats: Five cases. J. Feline Med. Surg. 2016, 18, 518–525. [Google Scholar] [CrossRef] [PubMed]
- Kinnunen, P.M.; Holopainen, J.M.; Hemmila, H.; Piiparinen, H.; Sironen, T.; Kivela, T.; Virtanen, J.; Niemimaa, J.; Nikkari, S.; Jarvinen, A.; et al. Severe ocular cowpox in a human, Finland. Emerg. Infect. Dis. 2015, 21, 2261–2263. [Google Scholar] [CrossRef] [PubMed]
- Baxby, D.; Bennett, M. Cowpox: A re-evaluation of the risks of human cowpox based on new epidemiological information. Arch. Virol. Suppl. 1997, 13, 1–12. [Google Scholar] [PubMed]
- Czerny, C.P.; Eis-Hubinger, A.M.; Mayr, A.; Schneweis, K.E.; Pfeiff, B. Animal poxviruses transmitted from cat to man: Current event with lethal end. Zentralbl. Veterinarmed. B 1991, 38, 421–431. [Google Scholar] [CrossRef] [PubMed]
- Pelkonen, P.M.; Tarvainen, K.; Hynninen, A.; Kallio, E.R.; Henttonen, K.; Palva, A.; Vaheri, A.; Vapalahti, O. Cowpox with severe generalized eruption, Finland. Emerg. Infect. Dis. 2003, 9, 1458–1461. [Google Scholar] [CrossRef] [PubMed]
- Kroon, E.G.; Mota, B.E.; Abrahao, J.S.; da Fonseca, F.G.; de Souza Trindade, G. Zoonotic Brazilian vaccinia virus: From field to therapy. Antivir. Res. 2011, 92, 150–163. [Google Scholar] [CrossRef] [PubMed]
- Singh, R.K.; Balamurugan, V.; Bhanuprakash, V.; Venkatesan, G.; Hosamani, M. Emergence and reemergence of vaccinia-like viruses: Global scenario and perspectives. Indian J. Virol. 2012, 23, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Singh, R.K.; Hosamani, M.; Balamurugan, V.; Bhanuprakash, V.; Rasool, T.J.; Yadav, M.P. Buffalopox: An emerging and re-emerging zoonosis. Anim. Health Res. Rev. 2007, 8, 105–114. [Google Scholar] [CrossRef] [PubMed]
- Damaso, C.R.; Esposito, J.J.; Condit, R.C.; Moussatche, N. An emergent poxvirus from humans and cattle in Rio de Janeiro State: Cantagalo virus may derive from Brazilian smallpox vaccine. Virology 2000, 277, 439–449. [Google Scholar] [CrossRef] [PubMed]
- De Souza Trindade, G.; da Fonseca, F.G.; Marques, J.T.; Nogueira, M.L.; Mendes, L.C.; Borges, A.S.; Peiro, J.R.; Pituco, E.M.; Bonjardim, C.A.; Ferreira, P.C.; et al. Aracatuba virus: A vaccinialike virus associated with infection in humans and cattle. Emerg. Infect. Dis. 2003, 9, 155–160. [Google Scholar] [CrossRef] [PubMed]
- Abrahao, J.S.; Campos, R.K.; Trindade Gde, S.; Guimaraes da Fonseca, F.; Ferreira, P.C.; Kroon, E.G. Outbreak of severe zoonotic vaccinia virus infection, Southeastern Brazil. Emerg. Infect. Dis. 2015, 21, 695–698. [Google Scholar] [CrossRef] [PubMed]
- Campos, R.K.; Brum, M.C.; Nogueira, C.E.; Drumond, B.P.; Alves, P.A.; Siqueira-Lima, L.; Assis, F.L.; Trindade, G.S.; Bonjardim, C.A.; Ferreira, P.C.; et al. Assessing the variability of Brazilian vaccinia virus isolates from a horse exanthematic lesion: Coinfection with distinct viruses. Arch. Virol. 2011, 156, 275–283. [Google Scholar] [CrossRef] [PubMed]
- Leite, J.A.; Drumond, B.P.; Trindade, G.S.; Lobato, Z.I.; da Fonseca, F.G.; dos Santos, J.R.; Madureira, M.C.; Guedes, M.I.; Ferreira, J.M.; Bonjardim, C.A.; et al. Passatempo virus, a vaccinia virus strain, Brazil. Emerg. Infect. Dis. 2005, 11, 1935–1938. [Google Scholar] [CrossRef] [PubMed]
- Abrahao, J.S.; Guedes, M.I.; Trindade, G.S.; Fonseca, F.G.; Campos, R.K.; Mota, B.F.; Lobato, Z.I.; Silva-Fernandes, A.T.; Rodrigues, G.O.; Lima, L.S.; et al. One more piece in the VACV ecological puzzle: Could peridomestic rodents be the link between wildlife and bovine vaccinia outbreaks in Brazil? PLoS ONE 2009, 4, e7428. [Google Scholar] [CrossRef] [PubMed]
- Abrahao, J.S.; Silva-Fernandes, A.T.; Lima, L.S.; Campos, R.K.; Guedes, M.I.; Cota, M.M.; Assis, F.L.; Borges, I.A.; Souza-Junior, M.F.; Lobato, Z.I.; et al. Vaccinia virus infection in monkeys, Brazilian Amazon. Emerg. Infect. Dis. 2010, 16, 976–979. [Google Scholar] [CrossRef] [PubMed]
- Franco-Luiz, A.P.; Fagundes-Pereira, A.; Costa, G.B.; Alves, P.A.; Oliveira, D.B.; Bonjardim, C.A.; Ferreira, P.C.; Trindade Gde, S.; Panei, C.J.; Galosi, C.M.; et al. Spread of vaccinia virus to cattle herds, Argentina, 2011. Emerg. Infect. Dis. 2014, 20, 1576–1578. [Google Scholar] [CrossRef] [PubMed]
- Franco-Luiz, A.P.; Oliveira, D.B.; Pereira, A.F.; Gasparini, M.C.; Bonjardim, C.A.; Ferreira, P.C.; Trindade, G.S.; Puentes, R.; Furtado, A.; Abrahao, J.S.; et al. Detection of vaccinia virus in dairy cattle serum samples from 2009, Uruguay. Emerg. Infect. Dis. 2016, 22, 2174–2177. [Google Scholar] [CrossRef] [PubMed]
- Usme-Ciro, J.A.; Paredes, A.; Walteros, D.M.; Tolosa-Perez, E.N.; Laiton-Donato, K.; Pinzon, M.D.; Petersen, B.W.; Gallardo-Romero, N.F.; Li, Y.; Wilkins, K.; et al. Detection and molecular characterization of zoonotic poxviruses circulating in the Amazon region of Colombia, 2014. Emerg. Infect. Dis. 2017, 23, 649–653. [Google Scholar] [CrossRef] [PubMed]
- Springer, Y.P.; Hsu, C.H.; Werle, Z.R.; Olson, L.E.; Cooper, M.P.; Castrodale, L.J.; Fowler, N.; McCollum, A.M.; Goldsmith, C.S.; Emerson, G.L.; et al. Novel orthopoxvirus infection in an Alaska resident. Clin. Infect. Dis. 2017, 64, 1737–1741. [Google Scholar] [CrossRef] [PubMed]
- Vora, N.M.; Li, Y.; Geleishvili, M.; Emerson, G.L.; Khmaladze, E.; Maghlakelidze, G.; Navdarashvili, A.; Zakhashvili, K.; Kokhreidze, M.; Endeladze, M.; et al. Human infection with a zoonotic orthopoxvirus in the country of Georgia. N. Engl. J. Med. 2015, 372, 1223–1230. [Google Scholar] [CrossRef] [PubMed]
- Cardeti, G.; Gruber, C.E.M.; Eleni, C.; Carletti, F.; Castilletti, C.; Manna, G.; Rosone, F.; Giombini, E.; Selleri, M.; Lapa, D.; et al. Fatal outbreak in Tonkean macaques caused by possibly novel orthopoxvirus, Italy, January 2015. Emerg. Infect. Dis. 2017, 23, 1941–1949. [Google Scholar] [CrossRef] [PubMed]
- Downie, A.W. Immunological relationship of the virus of spontaneous cowpox to vaccinia virus. Br. J. Exp. Pathol. 1939, 20, 158–176. [Google Scholar]
- Schrick, L.; Tausch, S.H.; Dabrowski, P.W.; Damaso, C.R.; Esparza, J.; Nitsche, A. An early American smallpox vaccine based on horsepox. N. Engl. J. Med. 2017, 377, 1491–1492. [Google Scholar] [CrossRef] [PubMed]
- Baxby, D. Jenner’s Smallpox Vaccine. The Riddle of the Origin of Vaccinia Virus; Heinemann: London, UK, 1981. [Google Scholar]
- Esparza, J.; Schrick, L.; Damaso, C.R.; Nitsche, A. Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine. Vaccine 2017, 35, 7222–7230. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Sampedro, L.; Perdiguero, B.; Mejias-Perez, E.; Garcia-Arriaza, J.; Di Pilato, M.; Esteban, M. The evolution of poxvirus vaccines. Viruses 2015, 7, 1726–1803. [Google Scholar] [CrossRef] [PubMed]
- Lane, J.M.; Ruben, F.L.; Neff, J.M.; Millar, J.D. Complications of smallpox vaccination, 1968. National surveillance in the United States. N. Engl. J. Med. 1969, 281, 1201–1208. [Google Scholar] [CrossRef] [PubMed]
- Greenberg, R.N.; Kennedy, J.S. ACAM2000: A newly licensed cell culture-based live vaccinia smallpox vaccine. Expert Opin. Investig. Drugs 2008, 17, 555–564. [Google Scholar] [CrossRef] [PubMed]
- Petersen, B.W.; Harms, T.J.; Reynolds, M.G.; Harrison, L.H. Use of vaccinia virus smallpox vaccine in laboratory and health care personnel at risk for occupational exposure to orthopoxviruses—recommendations of the advisory committee on immunization practices (ACIP), 2015. MMWR Morb. Mortal. Wkly. Rep. 2016, 65, 257–262. [Google Scholar] [CrossRef] [PubMed]
- Hashizume, S.; Yoshizawa, H.; Morita, M.; Suzuki, K. Properties of attenuated mutant of vaccinia virus, LC16m8, derived from Lister strain. In Vaccinia Viruses as Vectors for Vaccine Antigens; Quinnan, G.V., Ed.; Elsevier Science Publishing Co.: New York, NY, USA, 1985; pp. 87–99. [Google Scholar]
- Mayr, A.; Hochstein-Mintzel, V.; Stickl, H. Abstammung, eigenschaftenund verwendung des attenuierten vaccinia-stammes MVA. Infection 1975, 3, 6–16. [Google Scholar] [CrossRef]
- Meyer, H.; Sutter, G.; Mayr, A. Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. J. Gen. Virol. 1991, 72, 1031–1038. [Google Scholar] [CrossRef] [PubMed]
- Antoine, G.; Scheiflinger, F.; Dorner, F.; Falkner, F.G. The complete genomic sequence of the modified vaccinia Ankara strain: Comparison with other orthopoxviruses. Virology 1998, 244, 365–396. [Google Scholar] [CrossRef] [PubMed]
- Sutter, G.; Moss, B. Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc. Natl. Acad. Sci. USA 1992, 89, 10847–10851. [Google Scholar] [CrossRef] [PubMed]
- Blanchard, T.J.; Alcami, A.; Andrea, P.; Smith, G.L. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: Implications for use as a human vaccine. J. Gen. Virol. 1998, 79, 1159–1167. [Google Scholar] [CrossRef] [PubMed]
- Mayr, A. Smallpox vaccination and bioterrorism with pox viruses. Comp. Immunol. Microbiol. Infect. Dis. 2003, 26, 423–430. [Google Scholar] [CrossRef]
- Petersen, B.W.; Damon, I.K.; Pertowski, C.A.; Meaney-Delman, D.; Guarnizo, J.T.; Beigi, R.H.; Edwards, K.M.; Fisher, M.C.; Frey, S.E.; Lynfield, R.; et al. Clinical guidance for smallpox vaccine use in a postevent vaccination program. MMWR Recomm. Rep. 2015, 64, 1–26. [Google Scholar] [PubMed]
- Meseda, C.A.; Garcia, A.D.; Kumar, A.; Mayer, A.E.; Manischewitz, J.; King, L.R.; Golding, H.; Merchlinsky, M.; Weir, J.P. Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine Dryvax in a mouse model. Virology 2005, 339, 164–175. [Google Scholar] [CrossRef] [PubMed]
- Wyatt, L.S.; Earl, P.L.; Eller, L.A.; Moss, B. Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge. Proc. Natl. Acad. Sci. USA 2004, 101, 4590–4595. [Google Scholar] [CrossRef] [PubMed]
- Davies, D.H.; Wyatt, L.S.; Newman, F.K.; Earl, P.L.; Chun, S.; Hernandez, J.E.; Molina, D.M.; Hirst, S.; Moss, B.; Frey, S.E.; et al. Antibody profiling by proteome microarray reveals the immunogenicity of the attenuated smallpox vaccine modified vaccinia virus Ankara is comparable to that of Dryvax. J. Virol. 2008, 82, 652–663. [Google Scholar] [CrossRef] [PubMed]
- Takahashi-Nishimaki, F.; Funahashi, S.; Miki, K.; Hashizume, S.; Sugimoto, M. Regulation of plaque size and host range by a vaccinia virus gene related to complement system proteins. Virology 1991, 181, 158–164. [Google Scholar] [CrossRef]
- Johnson, B.F.; Kanatani, Y.; Fujii, T.; Saito, T.; Yokote, H.; Smith, G.L. Serological responses in humans to the smallpox vaccine LC16m8. J. Gen. Virol. 2011, 92, 2405–2410. [Google Scholar] [CrossRef] [PubMed]
- Putz, M.M.; Midgley, C.M.; Law, M.; Smith, G.L. Quantification of antibody responses against multiple antigens of the two infectious forms of vaccinia virus provides a benchmark for smallpox vaccination. Nat. Med. 2006, 12, 1310–1315. [Google Scholar] [CrossRef] [PubMed]
- Tartaglia, J.; Perkus, M.E.; Taylor, J.; Norton, E.K.; Audonnet, J.C.; Cox, W.I.; Davis, S.W.; van der Hoeven, J.; Meignier, B.; Riviere, M.; et al. NYVAC: A highly attenuated strain of vaccinia virus. Virology 1992, 188, 217–232. [Google Scholar] [CrossRef]
- Najera, J.L.; Gomez, C.E.; Domingo-Gil, E.; Gherardi, M.M.; Esteban, M. Cellular and biochemical differences between two attenuated poxvirus vaccine candidates (MVA and NYVAC) and role of the C7L gene. J. Virol. 2006, 80, 6033–6047. [Google Scholar] [CrossRef] [PubMed]
- Paoletti, E.; Tartaglia, J.; Taylor, J. Safe and effective poxvirus vectors—NYVAC and ALVAC. Dev. Biol. Stand. 1994, 82, 65–69. [Google Scholar] [PubMed]
- Tartaglia, J.; Cox, W.I.; Pincus, S.; Paoletti, E. Safety and immunogenicity of recombinants based on the genetically-engineered vaccinia strain, NYVAC. Dev. Biol. Stand. 1994, 82, 125–129. [Google Scholar] [PubMed]
- Smith, G.L.; Benfield, C.T.; Maluquer de Motes, C.; Mazzon, M.; Ember, S.W.; Ferguson, B.J.; Sumner, R.P. Vaccinia virus immune evasion: Mechanisms, virulence and immunogenicity. J. Gen. Virol. 2013, 94, 2367–2392. [Google Scholar] [CrossRef] [PubMed]
- Mansur, D.S.; Smith, G.L.; Ferguson, B.J. Intracellular sensing of viral DNA by the innate immune system. Microbes Infect. 2014, 16, 1002–1012. [Google Scholar] [CrossRef] [PubMed]
- Paludan, S.R.; Bowie, A.G. Immune sensing of DNA. Immunity 2013, 38, 870–880. [Google Scholar] [CrossRef] [PubMed]
- Wathelet, M.G.; Lin, C.H.; Parekh, B.S.; Ronco, L.V.; Howley, P.M.; Maniatis, T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol. Cell 1998, 1, 507–518. [Google Scholar] [CrossRef]
- Medzhitov, R. Recognition of microorganisms and activation of the immune response. Nature 2007, 449, 819–826. [Google Scholar] [CrossRef] [PubMed]
- Rot, A.; von Andrian, U.H. Chemokines in innate and adaptive host defense: Basic chemokinese grammar for immune cells. Annu. Rev. Immunol. 2004, 22, 891–928. [Google Scholar] [CrossRef] [PubMed]
- Randall, R.E.; Goodbourn, S. Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 2008, 89, 1–47. [Google Scholar] [CrossRef] [PubMed]
- Bonilla, F.A.; Oettgen, H.C. Adaptive immunity. J. Allergy Clin. Immunol. 2010, 125, S33–S40. [Google Scholar] [CrossRef] [PubMed]
- Ricklin, D.; Hajishengallis, G.; Yang, K.; Lambris, J.D. Complement: A key system for immune surveillance and homeostasis. Nat. Immunol. 2010, 11, 785–797. [Google Scholar] [CrossRef] [PubMed]
- Lanier, L.L. NK cell recognition. Annu. Rev. Immunol. 2005, 23, 225–274. [Google Scholar] [CrossRef] [PubMed]
- Chapman, J.L.; Nichols, D.K.; Martinez, M.J.; Raymond, J.W. Animal models of orthopoxvirus infection. Vet. Pathol. 2010, 47, 852–870. [Google Scholar] [CrossRef] [PubMed]
- Reading, P.C.; Smith, G.L. A kinetic analysis of immune mediators in the lungs of mice infected with vaccinia virus and comparison with intradermal infection. J. Gen. Virol. 2003, 84, 1973–1983. [Google Scholar] [CrossRef] [PubMed]
- Alcami, A.; Smith, G.L. A soluble receptor for interleukin-1 beta encoded by vaccinia virus: A novel mechanism of virus modulation of the host response to infection. Cell 1992, 71, 153–167. [Google Scholar] [CrossRef]
- Williamson, J.D.; Reith, R.W.; Jeffrey, L.J.; Arrand, J.R.; Mackett, M. Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route. J. Gen. Virol. 1990, 71, 2761–2767. [Google Scholar] [CrossRef] [PubMed]
- Fenner, F. The clinical features and pathogenesis of mouse-pox (infectious ectromelia of mice). J. Pathol. Bacteriol. 1948, 60, 529–552. [Google Scholar] [CrossRef]
- Abboud, G.; Desai, P.; Dastmalchi, F.; Stanfield, J.; Tahiliani, V.; Hutchinson, T.E.; Salek-Ardakani, S. Tissue-specific programming of memory CD8 T cell subsets impacts protection against lethal respiratory virus infection. J. Exp. Med. 2016, 213, 2897–2911. [Google Scholar] [CrossRef] [PubMed]
- Bonduelle, O.; Duffy, D.; Verrier, B.; Combadiere, C.; Combadiere, B. Cutting edge: Protective effect of CX3CR1+ dendritic cells in a vaccinia virus pulmonary infection model. J. Immunol. 2012, 188, 952–956. [Google Scholar] [CrossRef] [PubMed]
- Rivera, R.; Hutchens, M.; Luker, K.E.; Sonstein, J.; Curtis, J.L.; Luker, G.D. Murine alveolar macrophages limit replication of vaccinia virus. Virology 2007, 363, 48–58. [Google Scholar] [CrossRef] [PubMed]
- Goulding, J.; Abboud, G.; Tahiliani, V.; Desai, P.; Hutchinson, T.E.; Salek-Ardakani, S. CD8 T cells use IFN-gamma to protect against the lethal effects of a respiratory poxvirus infection. J. Immunol. 2014, 192, 5415–5425. [Google Scholar] [CrossRef] [PubMed]
- Goulding, J.; Bogue, R.; Tahiliani, V.; Croft, M.; Salek-Ardakani, S. CD8 T cells are essential for recovery from a respiratory vaccinia virus infection. J. Immunol. 2012, 189, 2432–2440. [Google Scholar] [CrossRef] [PubMed]
- Hu, Z.; Molloy, M.J.; Usherwood, E.J. CD4(+) T-cell dependence of primary CD8(+) T-cell response against vaccinia virus depends upon route of infection and viral dose. Cell. Mol. Immunol. 2016, 13, 82–93. [Google Scholar] [CrossRef] [PubMed]
- Tscharke, D.C.; Smith, G.L. A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. J. Gen. Virol. 1999, 80, 2751–2755. [Google Scholar] [CrossRef] [PubMed]
- Jacobs, N.; Chen, R.A.; Gubser, C.; Najarro, P.; Smith, G.L. Intradermal immune response after infection with vaccinia virus. J. Gen. Virol. 2006, 87, 1157–1161. [Google Scholar] [CrossRef] [PubMed]
- Davies, M.L.; Parekh, N.J.; Kaminsky, L.W.; Soni, C.; Reider, I.E.; Krouse, T.E.; Fischer, M.A.; van Rooijen, N.; Rahman, Z.S.M.; Norbury, C.C. A systemic macrophage response is required to contain a peripheral poxvirus infection. PLoS Pathog. 2017, 13, e1006435. [Google Scholar] [CrossRef] [PubMed]
- Mota, B.E.; Gallardo-Romero, N.; Trindade, G.; Keckler, M.S.; Karem, K.; Carroll, D.; Campos, M.A.; Vieira, L.Q.; da Fonseca, F.G.; Ferreira, P.C.; et al. Adverse events post smallpox-vaccination: Insights from tail scarification infection in mice with Vaccinia virus. PLoS ONE 2011, 6, e18924. [Google Scholar] [CrossRef] [PubMed]
- Belyakov, I.M.; Earl, P.; Dzutsev, A.; Kuznetsov, V.A.; Lemon, M.; Wyatt, L.S.; Snyder, J.T.; Ahlers, J.D.; Franchini, G.; Moss, B.; et al. Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. Proc. Natl. Acad. Sci. USA 2003, 100, 9458–9463. [Google Scholar] [CrossRef] [PubMed]
- Edghill-Smith, Y.; Golding, H.; Manischewitz, J.; King, L.R.; Scott, D.; Bray, M.; Nalca, A.; Hooper, J.W.; Whitehouse, C.A.; Schmitz, J.E.; et al. Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat. Med. 2005, 11, 740–747. [Google Scholar] [CrossRef] [PubMed]
- Panchanathan, V.; Chaudhri, G.; Karupiah, G. Protective immunity against secondary poxvirus infection is dependent on antibody but not on CD4 or CD8 T-cell function. J. Virol. 2006, 80, 6333–6338. [Google Scholar] [CrossRef] [PubMed]
- Gillard, G.O.; Bivas-Benita, M.; Hovav, A.H.; Grandpre, L.E.; Panas, M.W.; Seaman, M.S.; Haynes, B.F.; Letvin, N.L. Thy1+ NK [corrected] cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes. PLoS Pathog. 2011, 7, e1002141. [Google Scholar] [CrossRef]
- Medeiros-Silva, D.C.; Dos Santos Moreira-Silva, E.A.; Assis Silva Gomes, J.; da Fonseca, F.G.; Correa-Oliveira, R. CD4 and CD8 T cells participate in the immune memory response against Vaccinia virus after a previous natural infection. Results Immunol. 2013, 3, 104–113. [Google Scholar] [CrossRef] [PubMed]
- Midgley, C.M.; Putz, M.M.; Weber, J.N.; Smith, G.L. Vaccinia virus strain NYVAC induces substantially lower and qualitatively different human antibody responses compared with strains Lister and Dryvax. J. Gen. Virol. 2008, 89, 2992–2997. [Google Scholar] [CrossRef] [PubMed]
- Puissant-Lubrano, B.; Bossi, P.; Gay, F.; Crance, J.M.; Bonduelle, O.; Garin, D.; Bricaire, F.; Autran, B.; Combadiere, B. Control of vaccinia virus skin lesions by long-term-maintained IFN-gamma+TNF-alpha+ effector/memory CD4+ lymphocytes in humans. J. Clin. Investig. 2010, 120, 1636–1644. [Google Scholar] [CrossRef] [PubMed]
- Bronson, L.H.; Parker, R.F. The neutralization of vaccine virus by immune serum: Titration by the intracerebral inoculation of mice. J. Bacteriol. 1941, 41, 56–57. [Google Scholar]
- McFadden, G. Poxvirus tropism. Nat. Rev. Microbiol. 2005, 3, 201–213. [Google Scholar] [CrossRef] [PubMed]
- Werden, S.J.; Rahman, M.M.; McFadden, G. Poxvirus host range genes. Adv. Virus Res. 2008, 71, 135–171. [Google Scholar] [PubMed]
- Beattie, E.; Kauffman, E.B.; Martinez, H.; Perkus, M.E.; Jacobs, B.L.; Paoletti, E.; Tartaglia, J. Host-range restriction of vaccinia virus E3L-specific deletion mutants. Virus Genes 1996, 12, 89–94. [Google Scholar] [CrossRef] [PubMed]
- Perkus, M.E.; Goebel, S.J.; Davis, S.W.; Johnson, G.P.; Limbach, K.; Norton, E.K.; Paoletti, E. Vaccinia virus host range genes. Virology 1990, 179, 276–286. [Google Scholar] [CrossRef]
- Backes, S.; Sperling, K.M.; Zwilling, J.; Gasteiger, G.; Ludwig, H.; Kremmer, E.; Schwantes, A.; Staib, C.; Sutter, G. Viral host-range factor C7 or K1 is essential for modified vaccinia virus Ankara late gene expression in human and murine cells, irrespective of their capacity to inhibit protein kinase R-mediated phosphorylation of eukaryotic translation initiation factor 2alpha. J. Gen. Virol. 2010, 91, 470–482. [Google Scholar] [PubMed]
- Meng, X.; Jiang, C.; Arsenio, J.; Dick, K.; Cao, J.; Xiang, Y. Vaccinia virus K1L and C7L inhibit antiviral activities induced by type I interferons. J. Virol. 2009, 83, 10627–10636. [Google Scholar] [CrossRef] [PubMed]
- Najera, J.L.; Gomez, C.E.; Garcia-Arriaza, J.; Sorzano, C.O.; Esteban, M. Insertion of vaccinia virus C7L host range gene into NYVAC-B genome potentiates immune responses against HIV-1 antigens. PLoS ONE 2010, 5, e11406. [Google Scholar] [CrossRef] [PubMed]
- Zhang, P.; Jacobs, B.L.; Samuel, C.E. Loss of protein kinase PKR expression in human HeLa cells complements the vaccinia virus E3L deletion mutant phenotype by restoration of viral protein synthesis. J. Virol. 2008, 82, 840–848. [Google Scholar] [CrossRef] [PubMed]
- Jentarra, G.M.; Heck, M.C.; Youn, J.W.; Kibler, K.; Langland, J.O.; Baskin, C.R.; Ananieva, O.; Chang, Y.; Jacobs, B.L. Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: Scarification vaccination. Vaccine 2008, 26, 2860–2872. [Google Scholar] [CrossRef] [PubMed]
- Vijaysri, S.; Jentarra, G.; Heck, M.C.; Mercer, A.A.; McInnes, C.J.; Jacobs, B.L. Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: Intra-nasal vaccination. Vaccine 2008, 26, 664–676. [Google Scholar] [CrossRef] [PubMed]
- Denzler, K.L.; Rice, A.D.; MacNeill, A.L.; Fukushima, N.; Lindsey, S.F.; Wallace, G.; Burrage, A.M.; Smith, A.J.; Manning, B.R.; Swetnam, D.M.; et al. The NYCBH vaccinia virus deleted for the innate immune evasion gene, E3L, protects rabbits against lethal challenge by rabbitpox virus. Vaccine 2011, 29, 7659–7669. [Google Scholar] [CrossRef] [PubMed]
- Denzler, K.L.; Schriewer, J.; Parker, S.; Werner, C.; Hartzler, H.; Hembrador, E.; Huynh, T.; Holechek, S.; Buller, R.M.; Jacobs, B.L. The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus. Vaccine 2011, 29, 9691–9696. [Google Scholar] [CrossRef] [PubMed]
- Denzler, K.L.; Babas, T.; Rippeon, A.; Huynh, T.; Fukushima, N.; Rhodes, L.; Silvera, P.M.; Jacobs, B.L. Attenuated NYCBH vaccinia virus deleted for the E3L gene confers partial protection against lethal monkeypox virus disease in cynomolgus macaques. Vaccine 2011, 29, 9684–9690. [Google Scholar] [CrossRef] [PubMed]
- Volz, A.; Jany, S.; Freudenstein, A.; Lantermann, M.; Ludwig, H.; Sutter, G. E3L and F1L gene functions modulate the protective capacity of modified vaccinia virus Ankara immunization in murine model of human smallpox. Viruses 2018, 10. [Google Scholar] [CrossRef] [PubMed]
- Bravo Cruz, A.G.; Han, A.; Roy, E.J.; Guzman, A.B.; Miller, R.J.; Driskell, E.A.; O’Brien, W.D., Jr.; Shisler, J.L. Deletion of the K1L gene results in a vaccinia virus that is less pathogenic due to muted innate immune responses, yet still elicits protective immunity. J. Virol. 2017, 91. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Wang, S.; Zhang, Q.; Tian, M.; Hou, J.; Wang, R.; Liu, C.; Ji, X.; Liu, Y.; Shao, Y. Deletion of C7L and K1L genes leads to significantly decreased virulence of recombinant vaccinia virus TianTan. PLoS ONE 2013, 8, e68115. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; McFadden, G. SAMD9 is an innate antiviral host factor with stress response properties that can be antagonized by poxviruses. J. Virol. 2015, 89, 1925–1931. [Google Scholar] [CrossRef] [PubMed]
- Meng, X.; Schoggins, J.; Rose, L.; Cao, J.; Ploss, A.; Rice, C.M.; Xiang, Y. C7L family of poxvirus host range genes inhibits antiviral activities induced by type I interferons and interferon regulatory factor 1. J. Virol. 2012, 86, 4538–4547. [Google Scholar] [CrossRef] [PubMed]
- Willis, K.L.; Langland, J.O.; Shisler, J.L. Viral double-stranded RNAs from vaccinia virus early or intermediate gene transcripts possess PKR activating function, resulting in NF-kappaB activation, when the K1 protein is absent or mutated. J. Biol. Chem. 2011, 286, 7765–7778. [Google Scholar] [CrossRef] [PubMed]
- Willis, K.L.; Patel, S.; Xiang, Y.; Shisler, J.L. The effect of the vaccinia K1 protein on the PKR-eIF2alpha pathway in RK13 and HeLa cells. Virology 2009, 394, 73–81. [Google Scholar] [CrossRef] [PubMed]
- Bravo Cruz, A.G.; Shisler, J.L. Vaccinia virus K1 ankyrin repeat protein inhibits NF-kappaB activation by preventing RelA acetylation. J. Gen. Virol. 2016, 97, 2691–2702. [Google Scholar] [PubMed]
- Shisler, J.L.; Jin, X.L. The vaccinia virus K1L gene product inhibits host NF-kappaB activation by preventing IkappaBalpha degradation. J. Virol. 2004, 78, 3553–3560. [Google Scholar] [CrossRef] [PubMed]
- Hammami, A.; Charpentier, T.; Smans, M.; Stager, S. IRF-5-mediated inflammation limits CD8+ T cell expansion by inducing HIF-1alpha and impairing dendritic cell functions during leishmania infection. PLoS Pathog. 2015, 11, e1004938. [Google Scholar] [CrossRef] [PubMed]
- Haring, J.S.; Badovinac, V.P.; Harty, J.T. Inflaming the CD8+ T cell response. Immunity 2006, 25, 19–29. [Google Scholar] [CrossRef] [PubMed]
- Richer, M.J.; Nolz, J.C.; Harty, J.T. Pathogen-specific inflammatory milieux tune the antigen sensitivity of CD8(+) T cells by enhancing T cell receptor signaling. Immunity 2013, 38, 140–152. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Sampedro, L.; Mejias-Perez, E.; CO, S.S.; Najera, J.L.; Esteban, M. NYVAC vector modified by C7L viral gene insertion improves T cell immune responses and effectiveness against leishmaniasis. Virus Res. 2016, 220, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Brandt, T.A.; Jacobs, B.L. Both carboxy- and amino-terminal domains of the vaccinia virus interferon resistance gene, E3L, are required for pathogenesis in a mouse model. J. Virol. 2001, 75, 850–856. [Google Scholar] [CrossRef] [PubMed]
- Chang, H.W.; Jacobs, B.L. Identification of a conserved motif that is necessary for binding of the vaccinia virus E3L gene products to double-stranded RNA. Virology 1993, 194, 537–547. [Google Scholar] [CrossRef] [PubMed]
- Kim, Y.G.; Muralinath, M.; Brandt, T.; Pearcy, M.; Hauns, K.; Lowenhaupt, K.; Jacobs, B.L.; Rich, A. A role for Z-DNA binding in vaccinia virus pathogenesis. Proc. Natl. Acad. Sci. USA 2003, 100, 6974–6979. [Google Scholar] [CrossRef] [PubMed]
- Chang, H.W.; Watson, J.C.; Jacobs, B.L. The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc. Natl. Acad. Sci. USA 1992, 89, 4825–4829. [Google Scholar] [CrossRef] [PubMed]
- Langland, J.O.; Jacobs, B.L. Inhibition of PKR by vaccinia virus: Role of the N- and C-terminal domains of E3L. Virology 2004, 324, 419–429. [Google Scholar] [CrossRef] [PubMed]
- Rivas, C.; Gil, J.; Melkova, Z.; Esteban, M.; Diaz-Guerra, M. Vaccinia virus E3L protein is an inhibitor of the interferon-induced 2–5A synthetase enzyme. Virology 1998, 243, 406–414. [Google Scholar] [CrossRef] [PubMed]
- Guerra, S.; Caceres, A.; Knobeloch, K.P.; Horak, I.; Esteban, M. Vaccinia virus E3 protein prevents the antiviral action of ISG15. PLoS Pathog. 2008, 4, e1000096. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marq, J.B.; Hausmann, S.; Luban, J.; Kolakofsky, D.; Garcin, D. The double-stranded RNA binding domain of the vaccinia virus E3L protein inhibits both RNA- and DNA-induced activation of interferon beta. J. Biol. Chem. 2009, 284, 25471–25478. [Google Scholar] [CrossRef] [PubMed]
- Valentine, R.; Smith, G.L. Inhibition of the RNA polymerase III-mediated dsDNA-sensing pathway of innate immunity by vaccinia virus protein E3. J. Gen. Virol. 2010, 91, 2221–2229. [Google Scholar] [CrossRef] [PubMed]
- Koehler, H.; Cotsmire, S.; Langland, J.; Kibler, K.V.; Kalman, D.; Upton, J.W.; Mocarski, E.S.; Jacobs, B.L. Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the vaccinia virus innate immune evasion protein, E3. Proc. Natl. Acad. Sci. USA 2017, 114, 11506–11511. [Google Scholar] [CrossRef] [PubMed]
- Deng, L.; Dai, P.; Parikh, T.; Cao, H.; Bhoj, V.; Sun, Q.; Chen, Z.; Merghoub, T.; Houghton, A.; Shuman, S. Vaccinia virus subverts a mitochondrial antiviral signaling protein-dependent innate immune response in keratinocytes through its double-stranded RNA binding protein, E3. J. Virol. 2008, 82, 10735–10746. [Google Scholar] [CrossRef] [PubMed]
- Langland, J.O.; Kash, J.C.; Carter, V.; Thomas, M.J.; Katze, M.G.; Jacobs, B.L. Suppression of proinflammatory signal transduction and gene expression by the dual nucleic acid binding domains of the vaccinia virus E3L proteins. J. Virol. 2006, 80, 10083–10095. [Google Scholar] [CrossRef] [PubMed]
- Myskiw, C.; Arsenio, J.; van Bruggen, R.; Deschambault, Y.; Cao, J. Vaccinia virus E3 suppresses expression of diverse cytokines through inhibition of the PKR, NF-kappaB, and IRF3 pathways. J. Virol. 2009, 83, 6757–6768. [Google Scholar] [CrossRef] [PubMed]
- Xiang, Y.; Condit, R.C.; Vijaysri, S.; Jacobs, B.; Williams, B.R.; Silverman, R.H. Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus. J. Virol. 2002, 76, 5251–5259. [Google Scholar] [CrossRef] [PubMed]
- Ludwig, H.; Suezer, Y.; Waibler, Z.; Kalinke, U.; Schnierle, B.S.; Sutter, G. Double-stranded RNA-binding protein E3 controls translation of viral intermediate RNA, marking an essential step in the life cycle of modified vaccinia virus Ankara. J. Gen. Virol. 2006, 87, 1145–1155. [Google Scholar] [CrossRef] [PubMed]
- Ng, A.; Tscharke, D.C.; Reading, P.C.; Smith, G.L. The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence. J. Gen. Virol. 2001, 82, 2095–2105. [Google Scholar] [CrossRef] [PubMed]
- Clark, R.H.; Kenyon, J.C.; Bartlett, N.W.; Tscharke, D.C.; Smith, G.L. Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy. J. Gen. Virol. 2006, 87, 29–38. [Google Scholar] [CrossRef] [PubMed]
- Tscharke, D.C.; Reading, P.C.; Smith, G.L. Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes. J. Gen. Virol. 2002, 83, 1977–1986. [Google Scholar] [CrossRef] [PubMed]
- Spriggs, M.K.; Hruby, D.E.; Maliszewski, C.R.; Pickup, D.J.; Sims, J.E.; Buller, R.M.; VanSlyke, J. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Cell 1992, 71, 145–152. [Google Scholar] [CrossRef]
- Staib, C.; Kisling, S.; Erfle, V.; Sutter, G. Inactivation of the viral interleukin 1beta receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara. J. Gen. Virol. 2005, 86, 1997–2006. [Google Scholar] [CrossRef] [PubMed]
- Cottingham, M.G.; Andersen, R.F.; Spencer, A.J.; Saurya, S.; Furze, J.; Hill, A.V.; Gilbert, S.C. Recombination-mediated genetic engineering of a bacterial artificial chromosome clone of modified vaccinia virus Ankara (MVA). PLoS ONE 2008, 3, e1638. [Google Scholar] [CrossRef] [PubMed]
- Symons, J.A.; Adams, E.; Tscharke, D.C.; Reading, P.C.; Waldmann, H.; Smith, G.L. The vaccinia virus C12L protein inhibits mouse IL-18 and promotes virus virulence in the murine intranasal model. J. Gen. Virol. 2002, 83, 2833–2844. [Google Scholar] [CrossRef] [PubMed]
- Dai, K.; Liu, Y.; Liu, M.; Xu, J.; Huang, W.; Huang, X.; Liu, L.; Wan, Y.; Hao, Y.; Shao, Y. Pathogenicity and immunogenicity of recombinant Tiantan vaccinia virus with deleted C12L and A53R genes. Vaccine 2008, 26, 5062–5071. [Google Scholar] [CrossRef] [PubMed]
- Falivene, J.; Del Medico Zajac, M.P.; Pascutti, M.F.; Rodriguez, A.M.; Maeto, C.; Perdiguero, B.; Gomez, C.E.; Esteban, M.; Calamante, G.; Gherardi, M.M. Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. PLoS ONE 2012, 7, e32220. [Google Scholar] [CrossRef] [PubMed]
- Reading, P.C.; Symons, J.A.; Smith, G.L. A soluble chemokine-binding protein from vaccinia virus reduces virus virulence and the inflammatory response to infection. J. Immunol. 2003, 170, 1435–1442. [Google Scholar] [CrossRef] [PubMed]
- Symons, J.A.; Tscharke, D.C.; Price, N.; Smith, G.L. A study of the vaccinia virus interferon-gamma receptor and its contribution to virus virulence. J. Gen. Virol. 2002, 83, 1953–1964. [Google Scholar] [CrossRef] [PubMed]
- Verardi, P.H.; Jones, L.A.; Aziz, F.H.; Ahmad, S.; Yilma, T.D. Vaccinia virus vectors with an inactivated gamma interferon receptor homolog gene (B8R) are attenuated in vivo without a concomitant reduction in immunogenicity. J. Virol. 2001, 75, 11–18. [Google Scholar] [CrossRef] [PubMed]
- Symons, J.A.; Alcami, A.; Smith, G.L. Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity. Cell 1995, 81, 551–560. [Google Scholar] [CrossRef]
- Isaacs, S.N.; Kotwal, G.J.; Moss, B. Vaccinia virus complement-control protein prevents antibody-dependent complement-enhanced neutralization of infectivity and contributes to virulence. Proc. Natl. Acad. Sci. USA 1992, 89, 628–632. [Google Scholar] [CrossRef] [PubMed]
- Girgis, N.M.; Dehaven, B.C.; Xiao, Y.; Alexander, E.; Viner, K.M.; Isaacs, S.N. The vaccinia virus complement control protein modulates adaptive immune responses during infection. J. Virol. 2011, 85, 2547–2556. [Google Scholar] [CrossRef] [PubMed]
- Kotwal, G.J.; Moss, B. Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins. Nature 1988, 335, 176–178. [Google Scholar] [CrossRef] [PubMed]
- Kotwal, G.J.; Isaacs, S.N.; McKenzie, R.; Frank, M.M.; Moss, B. Inhibition of the complement cascade by the major secretory protein of vaccinia virus. Science 1990, 250, 827–830. [Google Scholar] [CrossRef] [PubMed]
- McKenzie, R.; Kotwal, G.J.; Moss, B.; Hammer, C.H.; Frank, M.M. Regulation of complement activity by vaccinia virus complement-control protein. J. Infect. Dis. 1992, 166, 1245–1250. [Google Scholar] [CrossRef] [PubMed]
- Bahar, M.W.; Kenyon, J.C.; Putz, M.M.; Abrescia, N.G.; Pease, J.E.; Wise, E.L.; Stuart, D.I.; Smith, G.L.; Grimes, J.M. Structure and function of A41, a vaccinia virus chemokine binding protein. PLoS Pathog. 2008, 4, e5. [Google Scholar] [CrossRef] [PubMed]
- Alcami, A.; Symons, J.A.; Collins, P.D.; Williams, T.J.; Smith, G.L. Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. J. Immunol. 1998, 160, 624–633. [Google Scholar] [PubMed]
- Graham, K.A.; Lalani, A.S.; Macen, J.L.; Ness, T.L.; Barry, M.; Liu, L.Y.; Lucas, A.; Clark-Lewis, I.; Moyer, R.W.; McFadden, G. The T1/35kDa family of poxvirus-secreted proteins bind chemokines and modulate leukocyte influx into virus-infected tissues. Virology 1997, 229, 12–24. [Google Scholar] [CrossRef] [PubMed]
- Patel, A.H.; Gaffney, D.F.; Subak-Sharpe, J.H.; Stow, N.D. DNA sequence of the gene encoding a major secreted protein of vaccinia virus, strain Lister. J. Gen. Virol. 1990, 71, 2013–2021. [Google Scholar] [CrossRef] [PubMed]
- Smith, C.A.; Smith, T.D.; Smolak, P.J.; Friend, D.; Hagen, H.; Gerhart, M.; Park, L.; Pickup, D.J.; Torrance, D.; Mohler, K.; et al. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology 1997, 236, 316–327. [Google Scholar] [CrossRef] [PubMed]
- Born, T.L.; Morrison, L.A.; Esteban, D.J.; VandenBos, T.; Thebeau, L.G.; Chen, N.; Spriggs, M.K.; Sims, J.E.; Buller, R.M. A poxvirus protein that binds to and inactivates IL-18, and inhibits NK cell response. J. Immunol. 2000, 164, 3246–3254. [Google Scholar] [CrossRef] [PubMed]
- Smith, V.P.; Bryant, N.A.; Alcami, A. Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins. J. Gen. Virol. 2000, 81, 1223–1230. [Google Scholar] [CrossRef] [PubMed]
- Reading, P.C.; Smith, G.L. Vaccinia virus interleukin-18-binding protein promotes virulence by reducing gamma interferon production and natural killer and T-cell activity. J. Virol. 2003, 77, 9960–9968. [Google Scholar] [CrossRef] [PubMed]
- Alcami, A.; Smith, G.L. A mechanism for the inhibition of fever by a virus. Proc. Natl. Acad. Sci. USA 1996, 93, 11029–11034. [Google Scholar] [CrossRef] [PubMed]
- Upton, C.; Mossman, K.; McFadden, G. Encoding of a homolog of the IFN-gamma receptor by myxoma virus. Science 1992, 258, 1369–1372. [Google Scholar] [CrossRef] [PubMed]
- Alcami, A.; Smith, G.L. Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity. J. Virol. 1995, 69, 4633–4639. [Google Scholar] [PubMed]
- Mossman, K.; Upton, C.; Buller, R.M.; McFadden, G. Species specificity of ectromelia virus and vaccinia virus interferon-gamma binding proteins. Virology 1995, 208, 762–769. [Google Scholar] [CrossRef] [PubMed]
- Alcami, A.; Smith, G.L. The vaccinia virus soluble interferon-gamma receptor is a homodimer. J. Gen. Virol. 2002, 83, 545–549. [Google Scholar] [CrossRef] [PubMed]
- Sroller, V.; Ludvikova, V.; Maresova, L.; Hainz, P.; Nemeckova, S. Effect of IFN-gamma receptor gene deletion on vaccinia virus virulence. Arch. Virol. 2001, 146, 239–249. [Google Scholar] [PubMed]
- Colamonici, O.R.; Domanski, P.; Sweitzer, S.M.; Larner, A.; Buller, R.M. Vaccinia virus B18R gene encodes a type I interferon-binding protein that blocks interferon alpha transmembrane signaling. J. Biol. Chem. 1995, 270, 15974–15978. [Google Scholar] [CrossRef] [PubMed]
- Smith, G.L.; Chan, Y.S. Two vaccinia virus proteins structurally related to the interleukin-1 receptor and the immunoglobulin superfamily. J. Gen. Virol. 1991, 72, 511–518. [Google Scholar] [CrossRef] [PubMed]
- Montanuy, I.; Alejo, A.; Alcami, A. Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses. FASEB J. 2011, 25, 1960–1971. [Google Scholar] [CrossRef] [PubMed]
- Alcami, A.; Symons, J.A.; Smith, G.L. The vaccinia virus soluble alpha/beta interferon (IFN) receptor binds to the cell surface and protects cells from the antiviral effects of IFN. J. Virol. 2000, 74, 11230–11239. [Google Scholar] [CrossRef] [PubMed]
- Gomez, C.E.; Perdiguero, B.; Najera, J.L.; Sorzano, C.O.; Jimenez, V.; Gonzalez-Sanz, R.; Esteban, M. Removal of vaccinia virus genes that block interferon type I and II pathways improves adaptive and memory responses of the HIV/AIDS vaccine candidate NYVAC-C in mice. J. Virol. 2012, 86, 5026–5038. [Google Scholar] [CrossRef] [PubMed]
- Alcami, A.; Khanna, A.; Paul, N.L.; Smith, G.L. Vaccinia virus strains Lister, USSR and Evans express soluble and cell-surface tumour necrosis factor receptors. J. Gen. Virol. 1999, 80, 949–959. [Google Scholar] [CrossRef] [PubMed]
- Reading, P.C.; Khanna, A.; Smith, G.L. Vaccinia virus CrmE encodes a soluble and cell surface tumor necrosis factor receptor that contributes to virus virulence. Virology 2002, 292, 285–298. [Google Scholar] [CrossRef] [PubMed]
- Brown, J.P.; Twardzik, D.R.; Marquardt, H.; Todaro, G.J. Vaccinia virus encodes a polypeptide homologous to epidermal growth factor and transforming growth factor. Nature 1985, 313, 491–492. [Google Scholar] [CrossRef] [PubMed]
- Buller, R.M.; Chakrabarti, S.; Cooper, J.A.; Twardzik, D.R.; Moss, B. Deletion of the vaccinia virus growth factor gene reduces virus virulence. J. Virol. 1988, 62, 866–874. [Google Scholar] [PubMed]
- Comeau, M.R.; Johnson, R.; DuBose, R.F.; Petersen, M.; Gearing, P.; VandenBos, T.; Park, L.; Farrah, T.; Buller, R.M.; Cohen, J.I.; et al. A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. Immunity 1998, 8, 473–482. [Google Scholar] [CrossRef]
- Gardner, J.D.; Tscharke, D.C.; Reading, P.C.; Smith, G.L. Vaccinia virus semaphorin A39R is a 50–55 kDa secreted glycoprotein that affects the outcome of infection in a murine intradermal model. J. Gen. Virol. 2001, 82, 2083–2093. [Google Scholar] [CrossRef] [PubMed]
- Chen, R.A.; Jacobs, N.; Smith, G.L. Vaccinia virus strain Western Reserve protein B14 is an intracellular virulence factor. J. Gen. Virol. 2006, 87, 1451–1458. [Google Scholar] [CrossRef] [PubMed]
- Kotwal, G.J.; Hugin, A.W.; Moss, B. Mapping and insertional mutagenesis of a vaccinia virus gene encoding a 13,800-Da secreted protein. Virology 1989, 171, 579–587. [Google Scholar] [CrossRef]
- Bartlett, N.; Symons, J.A.; Tscharke, D.C.; Smith, G.L. The vaccinia virus N1L protein is an intracellular homodimer that promotes virulence. J. Gen. Virol. 2002, 83, 1965–1976. [Google Scholar] [CrossRef] [PubMed]
- Maluquer de Motes, C.; Cooray, S.; Ren, H.; Almeida, G.M.; McGourty, K.; Bahar, M.W.; Stuart, D.I.; Grimes, J.M.; Graham, S.C.; Smith, G.L. Inhibition of apoptosis and NF-kappaB activation by vaccinia protein N1 occur via distinct binding surfaces and make different contributions to virulence. PLoS Pathog. 2011, 7, e1002430. [Google Scholar] [CrossRef] [PubMed]
- Ren, H.; Ferguson, B.J.; Maluquer de Motes, C.; Sumner, R.P.; Harman, L.E.; Smith, G.L. Enhancement of CD8(+) T-cell memory by removal of a vaccinia virus nuclear factor-kappaB inhibitor. Immunology 2015, 145, 34–49. [Google Scholar] [CrossRef] [PubMed]
- Benfield, C.T.; Ren, H.; Lucas, S.J.; Bahsoun, B.; Smith, G.L. Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection. J. Gen. Virol. 2013, 94, 1647–1657. [Google Scholar] [CrossRef] [PubMed]
- Harte, M.T.; Haga, I.R.; Maloney, G.; Gray, P.; Reading, P.C.; Bartlett, N.W.; Smith, G.L.; Bowie, A.; O’Neill, L.A. The poxvirus protein A52R targets Toll-like receptor signaling complexes to suppress host defense. J. Exp. Med. 2003, 197, 343–351. [Google Scholar] [CrossRef] [PubMed]
- Stack, J.; Haga, I.R.; Schroder, M.; Bartlett, N.W.; Maloney, G.; Reading, P.C.; Fitzgerald, K.A.; Smith, G.L.; Bowie, A.G. Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence. J. Exp. Med. 2005, 201, 1007–1018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Unterholzner, L.; Sumner, R.P.; Baran, M.; Ren, H.; Mansur, D.S.; Bourke, N.M.; Randow, F.; Smith, G.L.; Bowie, A.G. Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7. PLoS Pathog. 2011, 7, e1002247. [Google Scholar] [CrossRef] [PubMed]
- Sumner, R.P.; Ren, H.; Smith, G.L. Deletion of immunomodulator C6 from vaccinia virus strain Western Reserve enhances virus immunogenicity and vaccine efficacy. J. Gen. Virol. 2013, 94, 1121–1126. [Google Scholar] [CrossRef] [PubMed]
- Ferguson, B.J.; Benfield, C.T.; Ren, H.; Lee, V.H.; Frazer, G.L.; Strnadova, P.; Sumner, R.P.; Smith, G.L. Vaccinia virus protein N2 is a nuclear IRF3 inhibitor that promotes virulence. J. Gen. Virol. 2013, 94, 2070–2081. [Google Scholar] [CrossRef] [PubMed]
- Gerlic, M.; Faustin, B.; Postigo, A.; Yu, E.C.; Proell, M.; Gombosuren, N.; Krajewska, M.; Flynn, R.; Croft, M.; Way, M.; et al. Vaccinia virus F1L protein promotes virulence by inhibiting inflammasome activation. Proc. Natl. Acad. Sci. USA 2013, 110, 7808–7813. [Google Scholar] [CrossRef] [PubMed]
- Ember, S.W.; Ren, H.; Ferguson, B.J.; Smith, G.L. Vaccinia virus protein C4 inhibits NF-kappaB activation and promotes virus virulence. J. Gen. Virol. 2012, 93, 2098–2108. [Google Scholar] [CrossRef] [PubMed]
- Fahy, A.S.; Clark, R.H.; Glyde, E.F.; Smith, G.L. Vaccinia virus protein C16 acts intracellularly to modulate the host response and promote virulence. J. Gen. Virol. 2008, 89, 2377–2387. [Google Scholar] [CrossRef] [PubMed]
- Liu, S.W.; Katsafanas, G.C.; Liu, R.; Wyatt, L.S.; Moss, B. Poxvirus decapping enzymes enhance virulence by preventing the accumulation of dsRNA and the induction of innate antiviral responses. Cell Host Microbe 2015, 17, 320–331. [Google Scholar] [CrossRef] [PubMed]
- Strnadova, P.; Ren, H.; Valentine, R.; Mazzon, M.; Sweeney, T.R.; Brierley, I.; Smith, G.L. Inhibition of translation initiation by protein 169: A vaccinia virus strategy to suppress innate and adaptive immunity and alter virus virulence. PLoS Pathog. 2015, 11, e1005151. [Google Scholar] [CrossRef] [PubMed]
- Roper, R.L. Characterization of the vaccinia virus A35R protein and its role in virulence. J. Virol. 2006, 80, 306–313. [Google Scholar] [CrossRef] [PubMed]
- Rehm, K.E.; Jones, G.J.; Tripp, A.A.; Metcalf, M.W.; Roper, R.L. The poxvirus A35 protein is an immunoregulator. J. Virol. 2010, 84, 418–425. [Google Scholar] [CrossRef] [PubMed]
- Rehm, K.E.; Roper, R.L. Deletion of the A35 gene from modified vaccinia virus Ankara increases immunogenicity and isotype switching. Vaccine 2011, 29, 3276–3283. [Google Scholar] [CrossRef] [PubMed]
- Moore, J.B.; Smith, G.L. Steroid hormone synthesis by a vaccinia enzyme: A new type of virus virulence factor. EMBO J. 1992, 11, 1973–1980. [Google Scholar] [PubMed]
- Sroller, V.; Kutinova, L.; Nemeckova, S.; Simonova, V.; Vonka, V. Effect of 3-beta-hydroxysteroid dehydrogenase gene deletion on virulence and immunogenicity of different vaccinia viruses and their recombinants. Arch. Virol. 1998, 143, 1311–1320. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez, J.M.; Esteban, M. A poxvirus Bcl-2-like gene family involved in regulation of host immune response: Sequence similarity and evolutionary history. Virol. J. 2010, 7, 59. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goebel, S.J.; Johnson, G.P.; Perkus, M.E.; Davis, S.W.; Winslow, J.P.; Paoletti, E. The complete DNA sequence of vaccinia virus. Virology 1990, 179, 247–266, 517–563. [Google Scholar] [CrossRef]
- Smith, G.L.; Chan, Y.S.; Howard, S.T. Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the right inverted terminal repeat. J. Gen. Virol. 1991, 72, 1349–1376. [Google Scholar] [CrossRef] [PubMed]
- Aoyagi, M.; Zhai, D.; Jin, C.; Aleshin, A.E.; Stec, B.; Reed, J.C.; Liddington, R.C. Vaccinia virus N1L protein resembles a B cell lymphoma-2 (Bcl-2) family protein. Protein Sci. 2007, 16, 118–124. [Google Scholar] [CrossRef] [PubMed]
- Cooray, S.; Bahar, M.W.; Abrescia, N.G.; McVey, C.E.; Bartlett, N.W.; Chen, R.A.; Stuart, D.I.; Grimes, J.M.; Smith, G.L. Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein. J. Gen. Virol. 2007, 88, 1656–1666. [Google Scholar] [CrossRef] [PubMed]
- Graham, S.C.; Bahar, M.W.; Cooray, S.; Chen, R.A.; Whalen, D.M.; Abrescia, N.G.; Alderton, D.; Owens, R.J.; Stuart, D.I.; Smith, G.L.; et al. Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis. PLoS Pathog. 2008, 4, e1000128. [Google Scholar] [CrossRef] [PubMed]
- Kvansakul, M.; Yang, H.; Fairlie, W.D.; Czabotar, P.E.; Fischer, S.F.; Perugini, M.A.; Huang, D.C.; Colman, P.M. Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands. Cell Death Differ. 2008, 15, 1564–1571. [Google Scholar] [CrossRef] [PubMed]
- Fedosyuk, S.; Grishkovskaya, I.; de Almeida Ribeiro, E., Jr.; Skern, T. Characterization and structure of the vaccinia virus NF-kappaB antagonist A46. J. Biol. Chem. 2014, 289, 3749–3762. [Google Scholar] [CrossRef] [PubMed]
- Neidel, S.; Maluquer de Motes, C.; Mansur, D.S.; Strnadova, P.; Smith, G.L.; Graham, S.C. Vaccinia virus protein A49 is an unexpected member of the B-cell Lymphoma (Bcl)-2 protein family. J. Biol. Chem. 2015, 290, 5991–6002. [Google Scholar] [CrossRef] [PubMed]
- Kalverda, A.P.; Thompson, G.S.; Vogel, A.; Schroder, M.; Bowie, A.G.; Khan, A.R.; Homans, S.W. Poxvirus K7 protein adopts a Bcl-2 fold: Biochemical mapping of its interactions with human DEAD box RNA helicase DDX3. J. Mol. Biol. 2009, 385, 843–853. [Google Scholar] [CrossRef] [PubMed]
- Oda, S.; Schroder, M.; Khan, A.R. Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7. Structure 2009, 17, 1528–1537. [Google Scholar] [CrossRef] [PubMed]
- Stuart, J.H.; Sumner, R.P.; Lu, Y.; Snowden, J.S.; Smith, G.L. Vaccinia virus protein C6 inhibits type I IFN signalling in the nucleus and binds to the transactivation domain of STAT2. PLoS Pathog. 2016, 12, e1005955. [Google Scholar] [CrossRef] [PubMed]
- Chen, R.A.; Ryzhakov, G.; Cooray, S.; Randow, F.; Smith, G.L. Inhibition of IkappaB kinase by vaccinia virus virulence factor B14. PLoS Pathog. 2008, 4, e22. [Google Scholar] [CrossRef] [PubMed]
- McCoy, L.E.; Fahy, A.S.; Chen, R.A.; Smith, G.L. Mutations in modified virus Ankara protein 183 render it a non-functional counterpart of B14, an inhibitor of nuclear factor kappaB activation. J. Gen. Virol. 2010, 91, 2216–2220. [Google Scholar] [CrossRef] [PubMed]
- Benfield, C.T.; Mansur, D.S.; McCoy, L.E.; Ferguson, B.J.; Bahar, M.W.; Oldring, A.P.; Grimes, J.M.; Stuart, D.I.; Graham, S.C.; Smith, G.L. Mapping the IkappaB kinase beta (IKKbeta)-binding interface of the B14 protein, a vaccinia virus inhibitor of IKKbeta-mediated activation of nuclear factor kappaB. J. Biol. Chem. 2011, 286, 20727–20735. [Google Scholar] [CrossRef] [PubMed]
- DiPerna, G.; Stack, J.; Bowie, A.G.; Boyd, A.; Kotwal, G.; Zhang, Z.; Arvikar, S.; Latz, E.; Fitzgerald, K.A.; Marshall, W.L. Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors. J. Biol. Chem. 2004, 279, 36570–36578. [Google Scholar] [CrossRef] [PubMed]
- Mathew, A.; O’Bryan, J.; Marshall, W.; Kotwal, G.J.; Terajima, M.; Green, S.; Rothman, A.L.; Ennis, F.A. Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus. PLoS ONE 2008, 3, e3323. [Google Scholar] [CrossRef] [PubMed]
- Schroder, M.; Baran, M.; Bowie, A.G. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J. 2008, 27, 2147–2157. [Google Scholar] [CrossRef] [PubMed]
- Sumner, R.P.; Ren, H.; Ferguson, B.J.; Smith, G.L. Increased attenuation but decreased immunogenicity by deletion of multiple vaccinia virus immunomodulators. Vaccine 2016, 34, 4827–4834. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Arriaza, J.; Arnaez, P.; Gomez, C.E.; Sorzano, C.O.; Esteban, M. Improving adaptive and memory immune responses of an HIV/AIDS vaccine candidate MVA-B by deletion of vaccinia virus genes (C6L and K7R) blocking interferon signaling pathways. PLoS ONE 2013, 8, e66894. [Google Scholar] [CrossRef] [PubMed]
- Bowie, A.; Kiss-Toth, E.; Symons, J.A.; Smith, G.L.; Dower, S.K.; O’Neill, L.A. A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. Proc. Natl. Acad. Sci. USA 2000, 97, 10162–10167. [Google Scholar] [CrossRef] [PubMed]
- Di Pilato, M.; Mejias-Perez, E.; Sorzano, C.O.S.; Esteban, M. Distinct roles of vaccinia virus NF-kappaB inhibitor proteins A52, B15, and K7 in the immune response. J. Virol. 2017, 91. [Google Scholar] [CrossRef]
- Lysakova-Devine, T.; Keogh, B.; Harrington, B.; Nagpal, K.; Halle, A.; Golenbock, D.T.; Monie, T.; Bowie, A.G. Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46, specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF-related adaptor molecule. J. Immunol. 2010, 185, 4261–4271. [Google Scholar] [CrossRef]
- Stack, J.; Bowie, A.G. Poxviral protein A46 antagonizes Toll-like receptor 4 signaling by targeting BB loop motifs in Toll-IL-1 receptor adaptor proteins to disrupt receptor: Adaptor interactions. J. Biol. Chem. 2012, 287, 22672–22682. [Google Scholar] [CrossRef] [PubMed]
- Fedosyuk, S.; Bezerra, G.A.; Radakovics, K.; Smith, T.K.; Sammito, M.; Bobik, N.; Round, A.; Ten Eyck, L.F.; Djinovic-Carugo, K.; Uson, I.; et al. Vaccinia virus immunomodulator A46: A lipid and protein-binding scaffold for sequestering host TIR-domain proteins. PLoS Pathog. 2016, 12, e1006079. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Arriaza, J.; Najera, J.L.; Gomez, C.E.; Tewabe, N.; Sorzano, C.O.; Calandra, T.; Roger, T.; Esteban, M. A candidate HIV/AIDS vaccine (MVA-B) lacking vaccinia virus gene C6L enhances memory HIV-1-specific T-cell responses. PLoS ONE 2011, 6, e24244. [Google Scholar] [CrossRef] [PubMed]
- Garber, D.A.; O’Mara, L.A.; Gangadhara, S.; McQuoid, M.; Zhang, X.; Zheng, R.; Gill, K.; Verma, M.; Yu, T.; Johnson, B.; et al. Deletion of specific immune-modulatory genes from modified vaccinia virus Ankara-based HIV vaccines engenders improved immunogenicity in rhesus macaques. J. Virol. 2012, 86, 12605–12615. [Google Scholar] [CrossRef] [PubMed]
- Alharbi, N.K.; Spencer, A.J.; Hill, A.V.; Gilbert, S.C. Deletion of fifteen open reading frames from modified vaccinia virus Ankara fails to improve immunogenicity. PLoS ONE 2015, 10, e0128626. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Arriaza, J.; Gomez, C.E.; Sorzano, C.O.; Esteban, M. Deletion of the vaccinia virus N2L gene encoding an inhibitor of IRF3 improves the immunogenicity of modified vaccinia virus Ankara expressing HIV-1 antigens. J. Virol. 2014, 88, 3392–3410. [Google Scholar] [CrossRef] [PubMed]
- Postigo, A.; Cross, J.R.; Downward, J.; Way, M. Interaction of F1L with the BH3 domain of Bak is responsible for inhibiting vaccinia-induced apoptosis. Cell Death Differ. 2006, 13, 1651–1662. [Google Scholar] [CrossRef] [PubMed]
- Wasilenko, S.T.; Banadyga, L.; Bond, D.; Barry, M. The vaccinia virus F1L protein interacts with the proapoptotic protein Bak and inhibits Bak activation. J. Virol. 2005, 79, 14031–14043. [Google Scholar] [CrossRef] [PubMed]
- Yu, E.; Zhai, D.; Jin, C.; Gerlic, M.; Reed, J.C.; Liddington, R. Structural determinants of caspase-9 inhibition by the vaccinia virus protein, F1L. J. Biol. Chem. 2011, 286, 30748–30758. [Google Scholar] [CrossRef] [PubMed]
- Perdiguero, B.; Gomez, C.E.; Najera, J.L.; Sorzano, C.O.; Delaloye, J.; Gonzalez-Sanz, R.; Jimenez, V.; Roger, T.; Calandra, T.; Pantaleo, G.; et al. Deletion of the viral anti-apoptotic gene F1L in the HIV/AIDS vaccine candidate MVA-C enhances immune responses against HIV-1 antigens. PLoS ONE 2012, 7, e48524. [Google Scholar] [CrossRef] [PubMed]
- Peters, N.E.; Ferguson, B.J.; Mazzon, M.; Fahy, A.S.; Krysztofinska, E.; Arribas-Bosacoma, R.; Pearl, L.H.; Ren, H.; Smith, G.L. A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus. PLoS Pathog. 2013, 9, e1003649. [Google Scholar] [CrossRef] [PubMed]
- Ferguson, B.J.; Mansur, D.S.; Peters, N.E.; Ren, H.; Smith, G.L. DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. eLife 2012, 1, e00047. [Google Scholar] [CrossRef] [PubMed]
- Mazzon, M.; Peters, N.E.; Loenarz, C.; Krysztofinska, E.M.; Ember, S.W.; Ferguson, B.J.; Smith, G.L. A mechanism for induction of a hypoxic response by vaccinia virus. Proc. Natl. Acad. Sci. USA 2013, 110, 12444–12449. [Google Scholar] [CrossRef] [PubMed]
- Mazzon, M.; Castro, C.; Roberts, L.D.; Griffin, J.L.; Smith, G.L. A role for vaccinia virus protein C16 in reprogramming cellular energy metabolism. J. Gen. Virol. 2015, 96, 395–407. [Google Scholar] [CrossRef] [PubMed]
- Parrish, S.; Moss, B. Characterization of a vaccinia virus mutant with a deletion of the D10R gene encoding a putative negative regulator of gene expression. J. Virol. 2006, 80, 553–561. [Google Scholar] [CrossRef] [PubMed]
- Parrish, S.; Moss, B. Characterization of a second vaccinia virus mRNA-decapping enzyme conserved in poxviruses. J. Virol. 2007, 81, 12973–12978. [Google Scholar] [CrossRef] [PubMed]
- Rehm, K.E.; Connor, R.F.; Jones, G.J.; Yimbu, K.; Roper, R.L. Vaccinia virus A35R inhibits MHC class II antigen presentation. Virology 2010, 397, 176–186. [Google Scholar] [CrossRef] [PubMed]
- Yakubitskyi, S.N.; Kolosova, I.V.; Maksyutov, R.A.; Shchelkunov, S.N. Highly immunogenic variant of attenuated vaccinia virus. Dokl. Biochem. Biophys. 2016, 466, 35–38. [Google Scholar] [CrossRef] [PubMed]
- Blasco, R.; Cole, N.B.; Moss, B. Sequence analysis, expression, and deletion of a vaccinia virus gene encoding a homolog of profilin, a eukaryotic actin-binding protein. J. Virol. 1991, 65, 4598–4608. [Google Scholar] [PubMed]
- Douglass, N.J.; Blake, N.W.; Cream, J.J.; Soteriou, B.A.; Zhang, H.Y.; Theodoridou, A.; Archard, L.C. Similarity in genome organization between molluscum contagiosum virus (MCV) and vaccinia virus (VV): Identification of MCV homologues of the VV genes for protein kinase 2, structural protein VP8, RNA polymerase 35 kDa subunit and 3beta-hydroxysteroid dehydrogenase. J. Gen. Virol. 1996, 77, 3113–3120. [Google Scholar] [PubMed]
- Baker, M.E.; Blasco, R. Expansion of the mammalian 3 beta-hydroxysteroid dehydrogenase/plant dihydroflavonol reductase superfamily to include a bacterial cholesterol dehydrogenase, a bacterial UDP-galactose-4-epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus. FEBS Lett. 1992, 301, 89–93. [Google Scholar] [PubMed]
- Skinner, M.A.; Moore, J.B.; Binns, M.M.; Smith, G.L.; Boursnell, M.E. Deletion of fowlpox virus homologues of vaccinia virus genes between the 3 beta-hydroxysteroid dehydrogenase (A44L) and DNA ligase (A50R) genes. J. Gen. Virol. 1994, 75, 2495–2498. [Google Scholar] [CrossRef] [PubMed]
- Reading, P.C.; Moore, J.B.; Smith, G.L. Steroid hormone synthesis by vaccinia virus suppresses the inflammatory response to infection. J. Exp. Med. 2003, 197, 1269–1278. [Google Scholar] [CrossRef] [PubMed]
- Child, S.J.; Palumbo, G.J.; Buller, R.M.; Hruby, D.E. Insertional inactivation of the large subunit of ribonucleotide reductase encoded by vaccinia virus is associated with reduced virulence in vivo. Virology 1990, 174, 625–629. [Google Scholar] [CrossRef]
- Kan, S.; Jia, P.; Sun, L.; Hu, N.; Li, C.; Lu, H.; Tian, M.; Qi, Y.; Jin, N.; Li, X. Generation of an attenuated Tiantan vaccinia virus by deletion of the ribonucleotide reductase large subunit. Arch. Virol. 2014, 159, 2223–2231. [Google Scholar] [CrossRef] [PubMed]
- Buller, R.M.; Smith, G.L.; Cremer, K.; Notkins, A.L.; Moss, B. Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. Nature 1985, 317, 813–815. [Google Scholar] [CrossRef] [PubMed]
- Kasani, S.K.; Cheng, H.Y.; Yeh, K.H.; Chang, S.J.; Hsu, P.W.; Tung, S.Y.; Liang, C.T.; Chang, W. Differential innate immune signaling in macrophages by wild-type vaccinia mature virus and a mutant virus with a deletion of the A26 protein. J. Virol. 2017, 91. [Google Scholar] [CrossRef] [PubMed]
- Engelstad, M.; Smith, G.L. The vaccinia virus 42-kDa envelope protein is required for the envelopment and egress of extracellular virus and for virus virulence. Virology 1993, 194, 627–637. [Google Scholar] [CrossRef] [PubMed]
- Meseda, C.A.; Campbell, J.; Kumar, A.; Garcia, A.D.; Merchlinsky, M.; Weir, J.P. Effect of the deletion of genes encoding proteins of the extracellular virion form of vaccinia virus on vaccine immunogenicity and protective effectiveness in the mouse model. PLoS ONE 2013, 8, e67984. [Google Scholar] [CrossRef] [PubMed]
- Kettle, S.; Alcami, A.; Khanna, A.; Ehret, R.; Jassoy, C.; Smith, G.L. Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1beta-converting enzyme and protects virus-infected cells from TNF- and Fas-mediated apoptosis, but does not prevent IL-1beta-induced fever. J. Gen. Virol. 1997, 78, 677–685. [Google Scholar] [CrossRef] [PubMed]
- Kettle, S.; Blake, N.W.; Law, K.M.; Smith, G.L. Vaccinia virus serpins B13R (SPI-2) and B22R (SPI-1) encode M(r) 38.5 and 40K, intracellular polypeptides that do not affect virus virulence in a murine intranasal model. Virology 1995, 206, 136–147. [Google Scholar] [CrossRef]
- Zhou, J.; Crawford, L.; McLean, L.; Sun, X.Y.; Stanley, M.; Almond, N.; Smith, G.L. Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes. J. Gen. Virol. 1990, 71, 2185–2190. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.H.; Wilcock, D.; Smith, G.L. Vaccinia virus F12L protein is required for actin tail formation, normal plaque size, and virulence. J. Virol. 2000, 74, 11654–11662. [Google Scholar] [CrossRef] [PubMed]
- Parkinson, J.E.; Smith, G.L. Vaccinia virus gene A36R encodes a M(r) 43–50 K protein on the surface of extracellular enveloped virus. Virology 1994, 204, 376–390. [Google Scholar] [CrossRef] [PubMed]
- Wilcock, D.; Duncan, S.A.; Traktman, P.; Zhang, W.H.; Smith, G.L. The vaccinia virus A4OR gene product is a nonstructural, type II membrane glycoprotein that is expressed at the cell surface. J. Gen. Virol. 1999, 80, 2137–2148. [Google Scholar] [CrossRef] [PubMed]
- Kerr, S.M.; Johnston, L.H.; Odell, M.; Duncan, S.A.; Law, K.M.; Smith, G.L. Vaccinia DNA ligase complements Saccharomyces cerevisiae cdc9, localizes in cytoplasmic factories and affects virulence and virus sensitivity to DNA damaging agents. EMBO J. 1991, 10, 4343–4350. [Google Scholar] [PubMed]
- Beard, P.M.; Froggatt, G.C.; Smith, G.L. Vaccinia virus kelch protein A55 is a 64 kDa intracellular factor that affects virus-induced cytopathic effect and the outcome of infection in a murine intradermal model. J. Gen. Virol. 2006, 87, 1521–1529. [Google Scholar] [CrossRef] [PubMed]
- Froggatt, G.C.; Smith, G.L.; Beard, P.M. Vaccinia virus gene F3L encodes an intracellular protein that affects the innate immune response. J. Gen. Virol. 2007, 88, 1917–1921. [Google Scholar] [CrossRef] [PubMed]
- Pires de Miranda, M.; Reading, P.C.; Tscharke, D.C.; Murphy, B.J.; Smith, G.L. The vaccinia virus kelch-like protein C2L affects calcium-independent adhesion to the extracellular matrix and inflammation in a murine intradermal model. J. Gen. Virol. 2003, 84, 2459–2471. [Google Scholar] [CrossRef] [PubMed]
- Flexner, C.; Hugin, A.; Moss, B. Prevention of vaccinia virus infection in immunodeficient mice by vector-directed IL-2 expression. Nature 1987, 330, 259–262. [Google Scholar] [CrossRef] [PubMed]
- Ramshaw, I.A.; Andrew, M.E.; Phillips, S.M.; Boyle, D.B.; Coupar, B.E. Recovery of immunodeficient mice from a vaccinia virus/IL-2 recombinant infection. Nature 1987, 329, 545–546. [Google Scholar] [CrossRef] [PubMed]
- Sharma, D.P.; Ramsay, A.J.; Maguire, D.J.; Rolph, M.S.; Ramshaw, I.A. Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo. J. Virol. 1996, 70, 7103–7107. [Google Scholar] [PubMed]
- Verardi, P.H.; Legrand, F.A.; Chan, K.S.; Peng, Y.; Jones, L.A.; Yilma, T.D. IL-18 expression results in a recombinant vaccinia virus that is highly attenuated and immunogenic. J. Interferon Cytokine Res. 2014, 34, 169–178. [Google Scholar] [CrossRef] [PubMed]
- Giavedoni, L.D.; Jones, L.; Gardner, M.B.; Gibson, H.L.; Ng, C.T.; Barr, P.J.; Yilma, T. Vaccinia virus recombinants expressing chimeric proteins of human immunodeficiency virus and gamma interferon are attenuated for nude mice. Proc. Natl. Acad. Sci. USA 1992, 89, 3409–3413. [Google Scholar] [CrossRef] [PubMed]
- Kohonen-Corish, M.R.; King, N.J.; Woodhams, C.E.; Ramshaw, I.A. Immunodeficient mice recover from infection with vaccinia virus expressing interferon-gamma. Eur. J. Immunol. 1990, 20, 157–161. [Google Scholar] [CrossRef] [PubMed]
- Legrand, F.A.; Verardi, P.H.; Chan, K.S.; Peng, Y.; Jones, L.A.; Yilma, T.D. Vaccinia viruses with a serpin gene deletion and expressing IFN-gamma induce potent immune responses without detectable replication in vivo. Proc. Natl. Acad. Sci. USA 2005, 102, 2940–2945. [Google Scholar] [CrossRef] [PubMed]
- Bartlett, N.W.; Buttigieg, K.; Kotenko, S.V.; Smith, G.L. Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model. J. Gen. Virol. 2005, 86, 1589–1596. [Google Scholar] [CrossRef] [PubMed]
- Chavan, R.; Marfatia, K.A.; An, I.C.; Garber, D.A.; Feinberg, M.B. Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses. J. Virol. 2006, 80, 7676–7687. [Google Scholar] [CrossRef] [PubMed]
Protein | Function | Virulence (Mouse) | Virulence (Other Models) | Protective Efficacy/Immune Response | References | |||
---|---|---|---|---|---|---|---|---|
i.d. | i.n. | i.c. | Rabbit (i.d.) | Macaque (i.d.) | ||||
E3 | dsRNA-binding protein | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ protection (WR, NYCBH, MVA)n.c. CD8+ T-cell response | [128,129,130,131,132,133] |
K1 | NF-κB, PKR, IRF1 and type I IFN antagonist | ↓ | ↓ | ↑ protection (WR)n.c. CD8+ T-cell response | [134] | |||
C7 | PKR, IRF1 and type I IFN antagonist | n.c. | n.c. | [135] |
Protein | Function | Virulence | Protective Efficacy/Immune Response | References | ||
---|---|---|---|---|---|---|
i.d. | i.n. | i.c. | ||||
A41 | CC-chemokine binding protein | ↑ | ↑ | ↑ protection (MVA)↑ CD8+ T-cell response | [161,162] | |
B15 | IL-1β binding protein | n.c. | ↑ | ↓ | ↑ protection (MVA)↑ CD8+ T-cell response | [99,163,164,165,166] |
C12 | IL-18 binding protein | ↓ (rabbit skin) | ↓ | ↓ | ↑ protection (MVA) | [98,167,168,169] |
vCCI * | CC-chemokine binding protein | ↓ | [170] | |||
B8 | IFN-γ binding protein | ↓ (rabbit skin) | n.c./↓ | n.c. | [171,172] | |
B18 | type I IFN binding protein | ↓ | [173] | |||
C21, VCP | complement control protein | ↓ | ↑ protection (WR) | [174,175] |
Protein | Function | Virulence | Protective Efficacy/Immune Response | References | ||
---|---|---|---|---|---|---|
i.d. | i.n. | i.c. | ||||
B14 | NF-κB inhibitor | ↓ | n.c. | [204] | ||
N1 | NF-κB and apoptosis inhibitor | ↓ | ↓ | ↓ | ↑ protection (WR)↑ CD8+ T-cell response | [205,206,207,208] |
K7 | NF-κB and IRF3 inhibitor | ↓ | ↓ | ↑ protection (WR) | [209] | |
A52 | NF-κB inhibitor | ↓ | [210] | |||
A46 | NF-κB, IRF3 and MAPK inhibitor | ↓ | [211] | |||
C6 | IRF3 and JAK/STAT inhibitor | ↓ | ↓ | ↑ protection (WR)↑ CD8+ T-cell response | [212,213] | |
N2 | IRF3 inhibitor | ↓ | ↓ | n.c. protection (WR) | [214] | |
F1 | apoptosis and inflammasome inhibitor | ↓ | ↓ protection (MVA)n.c. CD8+ T-cell response | [133,215] |
Protein | Function | Virulence | Protective Efficacy/Immune Response | References | |||
---|---|---|---|---|---|---|---|
i.d. | i.n. | i.c. | i.p. | ||||
C4 | NF-κB inhibitor | n.c. | ↓ | [216] | |||
C16 | inhibitor of DNA sensing and promoter of hypoxic response | n.c. | ↓ | n.c. protection (WR) | [217] | ||
D9 | de-capping enzyme | n.c. | n.c. | n.c. protection (WR) | [218] | ||
D10 | de-capping enzyme | ↓ | ↓ | n.c. protection (WR) | [218] | ||
169 | inhibitor of translation | ↑ | ↑ | ↑ protection (WR)↑ CD8+ T-cell response | [219] | ||
A35 | inhibitor of MHC class II antigen presentation | ↓ | ↓ | ↑ protection (WR)n.c. protection (MVA) | [220,221,222] | ||
A44 | 3β-hydroxysteroid dehydrogenase | ↓ | ↓ | ↓ | [163,223,224] |
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Albarnaz, J.D.; Torres, A.A.; Smith, G.L. Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory. Viruses 2018, 10, 101. https://doi.org/10.3390/v10030101
Albarnaz JD, Torres AA, Smith GL. Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory. Viruses. 2018; 10(3):101. https://doi.org/10.3390/v10030101
Chicago/Turabian StyleAlbarnaz, Jonas D., Alice A. Torres, and Geoffrey L. Smith. 2018. "Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory" Viruses 10, no. 3: 101. https://doi.org/10.3390/v10030101