Inhibitors of Innate Immunity from Vaccinia Virus
Vaccinia virus (VACV) is an enigma, for it is the only vaccine to have eradicated a human disease, smallpox, and yet its origin and natural host remain unknown. After the eradication of smallpox, VACV has continued to be studied intensively because of the potential use of recombinant VACVs as vaccines against other infectious diseases, and because it is an excellent model for studying virus-host interactions. This short article considers some of the strategies used by VACV to suppress the host innate immune response to infection. These strategies include proteins that are secreted from infected cells to bind complement factors, cytokines, chemokines or interferons, and intracellular proteins that can synthesize steroid hormones, or block apoptosis or innate signalling pathways leading to production of inflammatory mediators.
KeywordsSynthesize Steroid Hormone Surface Groove Smallpox Vaccine Myxoma Virus Innate Immune Signalling
The author is most grateful to the conference organisers for the kind invitation to visit Israel and attend the 46th Oholo Conference. The work in the author’s laboratory has been supported by grants from the Wellcome Trust, the Medical Research Council of UK. GLS is a Wellcome Principal Research Fellow.
- 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. (2007) Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein. J Gen Virol, 88, 1656–66.PubMedCrossRefGoogle Scholar
- Diperna, G., Stack, J., Bowie, A. G., Boyd, A., Kotwal, G., Zhang, Z., Arvikar, S., Latz, E., Fitzgerald, K. A. & Marshall, W. L. (2004) 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, 279, 36570–8.PubMedCrossRefGoogle Scholar
- Downie, A. W. (1939) Immunological relationship of the virus of spontaneous cowpox to vaccinia virus. Br. J. Exp. Pathol., 20, 158–76.Google Scholar
- 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., Li, Y., Smith, G. L., Meyer, H., Leduc, J. W. & Wohlhueter, R. M. (2006) Genome sequence diversity and clues to the evolution of variola (smallpox) virus. Science, 313, 807–12.PubMedCrossRefGoogle Scholar
- Fenner, F., Anderson, D. A., Arita, I., Jezek, Z. & Ladnyi, I. D. (1988) Smallpox and Its Eradication, World Health Organisation, Geneva.Google Scholar
- Graham, S. C., Bahar, M. W., Cooray, S., Chen, R. A. J., Whalen, D. M., Abrescia, N. G. A., Alderton, D., Owens, R. J., Stuart, D. I., Smith, G. L. & Grimes, J. M. (2008) Vaccinia virus proteins A52 and B14 share a Bcl-2-like fold but have evolved to inhibit NF-kappa B rather than apoptosis. Plos Pathogens, 4, e100128.Google Scholar
- Hashizume, S., Yoshizawa, H., Morita, M. & Suzuki, K. (1985) Properties of attenuated mutant of vaccinia virus, LC16m8, derived from Lister strain. In Quinnan, G. V. (ed.), Vaccinia viruses as vectors for vaccine antigens. Elsevier, New York.Google Scholar
- Jenner, E. (1798) An Enquiry into the Causes and Effects of Variolae Vaccinae, a Disease Discovered in some Western Countries of England, particularly Gloucestershire, and known by the Name of Cow Pox., London, Reprinted by Cassell, 1896.Google Scholar
- Kvansakul, M., Yang, H., Fairlie, W. D., Czabotar, P. E., Fischer, S. F., Perugini, M. A., Huang, D. C. & Colman, P. M. (2008) 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, 15, 1564–71.PubMedCrossRefGoogle Scholar
- Moss, B. (2007) Poxviridae: the viruses and their replicaton. In Knipe, D. M. (ed.), Fields virology. 5th ed., Lippincott Williams & Wilkins, Philadelphia, PA.Google Scholar
- Smith, G. L., Murphy, B. R. & Moss, B. (1983b) Construction and characterization of an infectious vaccinia virus recombinant that expresses the influenza hemagglutinin gene and induces resistance to influenza virus infection in hamsters. Proc Natl Acad Sci USA, 80, 7155–9.PubMedCrossRefGoogle Scholar