About this Journal Submit a Manuscript Table of Contents 
Advances in Virology
Volume 2012 (2012), Article ID 524743, 17 pages
doi:10.1155/2012/524743
Review Article

Orthopoxvirus Genes That Mediate Disease Virulence and Host Tropism

Sergei N. Shchelkunov1,2

1Department of Genomic Research, State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region 630559, Russia
2Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia

Received 24 January 2012; Accepted 31 May 2012

Academic Editor: John Frater

Copyright © 2012 Sergei N. Shchelkunov. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. V. A. K. Rathinam and K. A. Fitzgerald, “Innate immune sensing of DNA viruses,” Virology, vol. 411, no. 2, pp. 153–162, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. K. A. Stoermer and T. E. Morrison, “Complement and viral pathogenesis,” Virology, vol. 411, no. 2, pp. 362–373, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. S. N. Shchelkunov, S. S. Marennikova, and R. W. Moyer, Orthopoxviruses Pathogenic for Humans, Springer, Berlin, Germany, 2005.
  4. S. N. Shchelkunov, “Emergence and reemergence of smallpox: the need in development of a new generation smallpox vaccine,” Vaccine, vol. 29, supplement 4, pp. D49–D53, 2011.
  5. S. N. Shchelkunov, “How long ago did smallpox virus emerge?” Archives of Virology, vol. 154, no. 12, pp. 1865–1871, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. I. V. Babkin and S. N. Shchelkunov, “Time scale of poxvirus evolution,” Molecular Biology, vol. 40, no. 1, pp. 16–19, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. B. Moss, et al., “Poxviridae: the viruses and their replication,” in Fields Virology, D. M. Knipe, P. M. Howley, D. E. Griffin, et al., Eds., pp. 2905–2946, Lippincott Williams and Wilkins, Philadelphia, Pa, USA, 2007.
  8. D. J. Esteban and R. M. L. Buller, “Ectromelia virus: the causative agent of mousepox,” Journal of General Virology, vol. 86, no. 10, pp. 2645–2659, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. J. L. Chapman, D. K. Nichols, M. J. Martinez, and J. W. Raymond, “Animal models of orthopoxvirus infection,” Veterinary Pathology, vol. 47, no. 5, pp. 852–870, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. F. Fenner, D. A. Henderson, I. Arita, Z. Jezek, and I. D. Ladnyi, Smallpox and Its Eradication, World Health Organization, Geneva, Switzerland, 1988.
  11. J. G. Breman, “Monkeypox: an emerging infection of humans?” in Emerging Infections 4, W. M. Scheid, W. A. Craig, and J. M. Hughes, Eds., pp. 45–67, ASM Press, Washington, DC, USA, 2000.
  12. A. W. Rimoin, P. M. Mulembakani, S. C. Johnston et al., “Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 37, pp. 16262–16267, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. R. M. Vorou, V. G. Papavassiliou, and I. N. Pierroutsakos, “Cowpox virus infection: an emerging health threat,” Current Opinion in Infectious Diseases, vol. 21, no. 2, pp. 153–156, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. H. Campe, P. Zimmermann, K. Glos et al., “Cowpox virus transmission from pet rats to humans, Germany,” Emerging Infectious Diseases, vol. 15, no. 5, pp. 777–780, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Ninove, Y. Domart, C. Vervel et al., “Cowpox virus transmission from pet rats to humans, France,” Emerging Infectious Diseases, vol. 15, no. 5, pp. 781–784, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Blackford, D. L. Roberts, and P. D. Thomas, “Cowpox infection causing a generalized eruption in a patient with atopic dermatitis,” British Journal of Dermatology, vol. 129, no. 5, pp. 628–629, 1993. View at Publisher · View at Google Scholar · View at Scopus
  17. P. M. Pelkonen, K. Tarvainen, A. Hynninen et al., “Cowpox with severe generalized eruption, Finland,” Emerging Infectious Diseases, vol. 9, no. 11, pp. 1458–1461, 2003. View at Scopus
  18. C. P. Czerny, A. M. Eis-Hübinger, A. Mayr, K. E. Schneweis, and B. Pfeiff, “Animal poxviruses transmitted from cat to man: current event with lethal end,” Zentralblatt fur Veterinarmedizin B, vol. 38, no. 6, pp. 421–431, 1991. View at Scopus
  19. R. K. Singh, M. Hosamani, V. Balamurugan, V. Bhanuprakash, T. J. Rasool, and M. P. Yadav, “Buffalopox: an emerging and re-emerging zoonosis,” Animal Health Research Reviews, vol. 8, no. 1, pp. 105–114, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. A. T. Silva-Fernandes, C. E. P. F. Travassos, J. M. S. Ferreira et al., “Natural human infections with vaccinia virus during bovine vaccinia outbreaks,” Journal of Clinical Virology, vol. 44, no. 4, pp. 308–313, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. J. S. Abrahão, M. I. M. Guedes, G. S. Trindade 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, vol. 4, no. 10, Article ID e7428, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. S. N. Shchelkunov, “Functional organization of variola major and vaccinia virus genomes,” Virus Genes, vol. 10, no. 1, pp. 53–71, 1995. View at Publisher · View at Google Scholar · View at Scopus
  23. S. N. Shchelkunov, P. F. Safronov, A. V. Totmenin et al., “The genomic sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins,” Virology, vol. 243, no. 2, pp. 432–460, 1998. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Kawai and S. Akira, “The role of pattern-recognition receptors in innate immunity: update on toll-like receptors,” Nature Immunology, vol. 11, no. 5, pp. 373–384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Lamkanfi and V. M. Dixit, “The inflammasomes,” PLoS Pathogens, vol. 5, no. 12, Article ID e1000510, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. A. A. Abdul-Sater, N. Saïd-Sadier, D. M. Ojcius, O. Yilmaz, and K. A. Kelly, “Inflammasomes bridge signaling between pathogen identification and the immune response,” Drugs of Today, vol. 45, pp. 105–112, 2009. View at Scopus
  27. J. H. Pedra, S. L. Cassel, and F. S. Sutterwala, “Sensing pathogens and danger signals by the inflammasome,” Current Opinion in Immunology, vol. 21, no. 1, pp. 10–16, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Bowie, E. Kiss-Toth, J. A. Symons, G. L. Smith, S. K. Dower, and L. A. J. O'Neill, “A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 18, pp. 10162–10167, 2000. View at Scopus
  29. M. T. Harte, I. R. Haga, G. Maloney et al., “The poxvirus protein A52R targets toll-like receptor signaling complexes to suppress host defense,” Journal of Experimental Medicine, vol. 197, no. 3, pp. 343–351, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Stack, I. R. Haga, M. Schröder et al., “Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence,” Journal of Experimental Medicine, vol. 201, no. 6, pp. 1007–1018, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. S. C. Graham, M. W. Bahar, S. Cooray et al., “Vaccinia virus proteins A52 and B14 share a Bcl-2-like fold but have evolved to inhibit Nf-κB rather than apoptosis,” PLoS Pathogens, vol. 4, no. 8, Article ID e1000128, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. J. M. Gonzlez and M. Esteban, “A poxvirus Bcl-2-like gene family involved in regulation of host immune response: sequence similarity and evolutionary history,” Virology Journal, vol. 7, article 59, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. L. Unterholzner, R. P. Sumner, M. Baran et al., “Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7,” PLoS Pathogens, vol. 7, no. 9, Article ID 100224, 2011.
  34. C. M. de Motes, S. Cooray, H. Ren et al., “Inhibition of apoptosis and NF-êB activation by vaccinia protein N1 occur via distinct binding surfaces and make different contributions to virulence,” PLoS Pathogens, vol. 7, no. 12, Article ID 100243, 2011.
  35. A. Ciechanover, “Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting,” Experimental Biology and Medicine, vol. 231, no. 7, pp. 1197–1211, 2006. View at Scopus
  36. D. R. Bosu and E. T. Kipreos, “Cullin-RING ubiquitin ligases: global regulation and activation cycles,” Cell Division, vol. 3, article e7, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Hochstrasser, “Origin and function of ubiquitin-like proteins,” Nature, vol. 458, no. 7237, pp. 422–429, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. E. T. Kipreos, L. E. Lander, J. P. Wing, W. W. He, and E. M. Hedgecock, “cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family,” Cell, vol. 85, no. 6, pp. 829–839, 1996. View at Publisher · View at Google Scholar · View at Scopus
  39. C. A. P. Joazeiro and A. M. Weissman, “RING finger proteins: mediators of ubiquitin ligase activity,” Cell, vol. 102, no. 5, pp. 549–552, 2000. View at Scopus
  40. E. T. Kipreos and M. Pagano, “The F-box protein family,” Genome Biology, vol. 1, no. 5, pp. reviews3002–reviews3002.7, 2000. View at Scopus
  41. J. Jin, T. Cardozo, R. C. Lovering, S. J. Elledge, M. Pagano, and J. W. Harper, “Systematic analysis and nomenclature of mammalian F-box proteins,” Genes and Development, vol. 18, no. 21, pp. 2573–2580, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. L. Pintard, A. Willems, and M. Peter, “Cullin-based ubiquitin ligases: Cul3-BTB complexes join the family,” The EMBO Journal, vol. 23, no. 8, pp. 1681–1687, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. P. J. Stogios, G. S. Downs, J. J. Jauhal, S. K. Nandra, and G. G. Privé, “Sequence and structural analysis of BTB domain proteins,” Genome Biology, vol. 6, no. 10, article R82, 2005. View at Scopus
  44. M. Furukawa and Y. Xiong, “BTB protein keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the cullin 3-Roc1 ligase,” Molecular and Cellular Biology, vol. 25, no. 1, pp. 162–171, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. G. Gao and H. Luo, “The ubiquitin-proteasome pathway in viral infections,” Canadian Journal of Physiology and Pharmacology, vol. 84, no. 1, pp. 5–14, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. M. J. Edelmann and B. M. Kessler, “Ubiquitin and ubiquitin-like specific proteases targeted by infectious pathogens: emerging patterns and molecular principles,” Biochimica et Biophysica Acta, vol. 1782, no. 12, pp. 809–816, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. H. A. Lindner, “Deubiquitination in virus infection,” Virology, vol. 362, no. 2, pp. 245–256, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. P. Blanchette and P. E. Branton, “Manipulation of the ubiquitin-proteasome pathway by small DNA tumor viruses,” Virology, vol. 384, no. 2, pp. 317–323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. N. Tolonen, L. Doglio, S. Schleich, and J. Krijnse Locker, “Vaccinia virus DNA replication occurs in endoplasmic reticulum-enclosed cytoplasmic mini-nuclei,” Molecular Biology of the Cell, vol. 12, no. 7, pp. 2031–2046, 2001. View at Scopus
  50. A. Teale, S. Campbell, N. Van Buuren et al., “Orthopoxviruses require a functional ubiquitin-proteasome system for productive replication,” Journal of Virology, vol. 83, no. 5, pp. 2099–2108, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. P. S. Satheshkumar, L. C. Anton, P. Sanz, and B. Moss, “Inhibition of the ubiquitin-proteasome system prevents vaccinia virus dna replication and expression of intermediate and late genes,” Journal of Virology, vol. 83, no. 6, pp. 2469–2479, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. C. S. Chung, C. H. Chen, M. Y. Ho, C. Y. Huang, C. L. Liao, and W. Chang, “Vaccinia virus proteome: identification of proteins in vaccinia virus intracellular mature virion particles,” Journal of Virology, vol. 80, no. 5, pp. 2127–2140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. R. B. Luftig, “Does the cytoskeleton play a significant role in animal virus replication?” Journal of Theoretical Biology, vol. 99, no. 1, pp. 173–191, 1982. View at Scopus
  54. A. Schepis, B. Schramm, C. A. M. de Haan, and J. K. Locker, “Vaccinia virus-induced microtubule-dependent cellular rearrangements,” Traffic, vol. 7, no. 3, pp. 308–323, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. P. M. Steinert and D. R. Roop, “Molecular and cellular biology of intermediate filaments,” Annual Review of Biochemistry, vol. 57, pp. 593–625, 1988. View at Scopus
  56. F. Fenner, R. Wittek, and K. R. Dumbell, The Orthopoxviruses, Academic Press, New York, NY, USA, 1989.
  57. M. S. Hayden and S. Ghosh, “Shared principles in NF-κB signaling,” Cell, vol. 132, no. 3, pp. 344–362, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. S. J. Chang, J. C. Hsiao, S. Sonnberg et al., “Poxvirus host range protein CP77 contains an F-box-like domain that is necessary to suppress NF-κB activation by tumor necrosis factor alpha but is independent of its host range function,” Journal of Virology, vol. 83, no. 9, pp. 4140–4152, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. J. L. Shisler and X. L. Jin, “The vaccinia virus K1L gene product inhibits host NF-κB activation by preventing IκBα degradation,” Journal of Virology, vol. 78, no. 7, pp. 3553–3560, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. S. E. Lux, K. M. John, and V. Bennett, “Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins,” Nature, vol. 344, no. 6261, pp. 36–42, 1990. View at Scopus
  61. S. Lambert, H. Yu, J. T. Prchal et al., “cDNA sequence for human erythrocyte ankyrin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 5, pp. 1730–1734, 1990. View at Scopus
  62. S. N. Shchelkunov, V. M. Blinov, and L. S. Sandakhchiev, “Ankyrin-like proteins of variola and vaccinia viruses,” FEBS Letters, vol. 319, no. 1-2, pp. 163–165, 1993. View at Publisher · View at Google Scholar · View at Scopus
  63. S. N. Shchelkunov, “Interaction of orthopoxviruses with the cellular ubiquitin-ligase system,” Virus Genes, vol. 41, no. 3, pp. 309–318, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. S. N. Shchelkunov, A. V. Totmenin, I. V. Babkin et al., “Human monkeypox and smallpox viruses: genomic comparison,” FEBS Letters, vol. 509, no. 1, pp. 66–70, 2001. View at Publisher · View at Google Scholar · View at Scopus
  65. C. Meisinger-Henschel, M. Schmidt, S. Lukassen et al., “Genomic sequence of chorioallantois vaccinia virus Ankara, the ancestor of modified vaccinia virus Ankara,” Journal of General Virology, vol. 88, no. 12, pp. 3249–3259, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. A. A. Mercer, S. B. Fleming, and N. Ueda, “F-box-like domains are present in most poxvirus ankyrin repeat proteins,” Virus Genes, vol. 31, no. 2, pp. 127–133, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Sonnberg, B. T. Seet, T. Pawson, S. B. Fleming, and A. A. Mercer, “Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 31, pp. 10955–10960, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. S. Sonnberg, S. B. Fleming, and A. A. Mercer, “A truncated two-α-helix F-box present in poxvirus ankyrin-repeat proteins is sufficient for binding the SCF1 ubiquitin ligase complex,” Journal of General Virology, vol. 90, no. 5, pp. 1224–1228, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. M. R. Mohamed, M. M. Rahman, J. S. Lanchbury et al., “Proteomic screening of variola virus reveals a unique NF-κB inhibitor that is highly conserved among pathogenic orthopoxviruses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 22, pp. 9045–9050, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. K. M. Sperling, A. Schwantes, C. Staib, B. S. Schnierle, and G. Sutter, “The orthopoxvirus 68-kilodalton ankyrin-like protein is essential for DNA replication and complete gene expression of modified vaccinia virus ankara in nonpermissive human and murine cells,” Journal of Virology, vol. 83, no. 12, pp. 6029–6038, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. N. van Buuren, B. Couturier, Y. Xiong, and M. Barry, “Ectromelia virus encodes a novel family of F-box proteins that interact with the SCF complex,” Journal of Virology, vol. 82, no. 20, pp. 9917–9927, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. T. G. Senkevich, G. L. Muravnik, S. G. Pozdnyakov et al., “Nucleotide sequence of XhoI fragment of ectromelia virus DNA reveals significant differences from vaccinia virus,” Virus Research, vol. 30, no. 1, pp. 73–88, 1993. View at Publisher · View at Google Scholar · View at Scopus
  73. S. N. Shchelkunov, V. M. Blinov, S. M. Resenchuk et al., “Analysis of the nucleotide sequence of 53 kbp from the right terminus of the genome of variola major virus strain India-1967,” Virus Research, vol. 34, no. 3, pp. 207–236, 1994. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Shchelkunov, A. Totmenin, and I. Kolosova, “Species-specific differences in organization of orthopoxvirus kelch-like proteins,” Virus Genes, vol. 24, no. 2, pp. 157–162, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. N. Chen, M. I. Danila, Z. Feng et al., “The genomic sequence of ectromelia virus, the causative agent of mousepox,” Virology, vol. 317, no. 1, pp. 165–186, 2003. View at Publisher · View at Google Scholar · View at Scopus
  76. M. E. Perkus, S. J. Goebel, S. W. Davis, G. P. Johnson, E. K. Norton, and E. Paoletti, “Deletion of 55 open reading frames from the termini of vaccinia virus,” Virology, vol. 180, no. 1, pp. 406–410, 1991. View at Publisher · View at Google Scholar · View at Scopus
  77. B. A. Wilton, S. Campbell, N. Van Buuren et al., “Ectromelia virus BTB/kelch proteins, EVM150 and EVM167, interact with cullin-3-based ubiquitin ligases,” Virology, vol. 374, no. 1, pp. 82–99, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. L. Zhang, N. Y. Villa, and G. McFadden, “Interplay between poxviruses and the cellular ubiquitin/ubiquitin-like pathways,” FEBS Letters, vol. 583, no. 4, pp. 607–614, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. G. V. Kochneva, I. V. Kolosova, T. A. Lupan et al., “Orthopoxvirus genes for kelch-like proteins: III. Construction of mousepox (ectromelia) virus variants with targeted gene deletions,” Molecular Biology, vol. 43, no. 4, pp. 567–572, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. G. Kochneva, I. Kolosova, T. Maksyutova, E. Ryabchikova, and S. Shchelkunov, “Effects of deletions of kelch-like genes on cowpox virus biological properties,” Archives of Virology, vol. 150, no. 9, pp. 1857–1870, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. G. V. Kochneva, O. S. Taranov, T. A. Lupan et al., “Investigation of the impact of cowpox virus BTB/kelch gene deletion on some characteristics of infection in vitro,” Voprosy Virusologii, vol. 54, no. 1, pp. 28–32, 2009. View at Scopus
  82. M. P. de Miranda, P. C. Reading, D. C. Tscharke, B. J. Murphy, and G. L. Smith, “The vaccinia virus kelch-like protein C2L affects calcium-independent adhesion to the extracellular matrix and inflammation in a murine intradermal model,” Journal of General Virology, vol. 84, no. 9, pp. 2459–2471, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. P. M. Beard, G. C. Froggatt, and G. L. Smith, “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,” Journal of General Virology, vol. 87, no. 6, pp. 1521–1529, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. G. C. Froggatt, G. L. Smith, and P. M. Beard, “Vaccinia virus gene F3L encodes an intracellular protein that affects the innate immune response,” Journal of General Virology, vol. 88, no. 7, pp. 1917–1921, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. J. F. Kerr, A. H. Wyllie, and A. R. Currie, “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics,” British Journal of Cancer, vol. 26, no. 4, pp. 239–257, 1972. View at Scopus
  86. M. R. Hilleman, “Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, supplement 2, pp. 14560–14566, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. E. Domingo-Gil and M. Esteban, “Role of mitochondria in apoptosis induced by the 2-5A system and mechanisms involved,” Apoptosis, vol. 11, no. 5, pp. 725–738, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. M. G. Netea, A. Simon, F. van de Veerdonk, B. J. Kullberg, J. W. M. van der Meer, and L. A. B. Joosten, “IL-1β processing in host defense: beyond the inflammasomes,” PLoS Pathogens, vol. 6, no. 2, Article ID e1000661, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. J. Macen, A. Takahashi, K. B. Moon, R. Nathaniel, P. C. Turner, and R. W. Moyer, “Activation of caspases in pig kidney cells infected with wild-type and CrmA/SPI-2 mutants of cowpox and rabbitpox viruses,” Journal of Virology, vol. 72, no. 5, pp. 3524–3533, 1998. View at Scopus
  90. B. T. Seet, J. B. Johnston, C. R. Brunetti et al., “Poxviruses and immune evasion,” Annual Review of Immunology, vol. 21, pp. 377–423, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. B. G. Luttge and R. W. Moyer, “Suppressors of a host range mutation in the rabbitpox virus serpin SPI-1 map to proteins essential for viral DNA replication,” Journal of Virology, vol. 79, no. 14, pp. 9168–9179, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. J. M. Taylor, D. Quilty, L. Banadyga, and M. Barry, “The vaccinia virus protein F1L interacts with Bim and inhibits activation of the pro-apoptotic protein Bax,” Journal of Biological Chemistry, vol. 281, no. 51, pp. 39728–39739, 2006. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Postigo, M. C. Martin, M. P. Dodding, and M. Way, “Vaccinia-induced epidermal growth factor receptor-MEK signalling and the anti-apoptotic protein F1L synergize to suppress cell death during infection,” Cellular Microbiology, vol. 11, no. 8, pp. 1208–1218, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Zhai, E. Yu, C. Jin et al., “Vaccinia virus protein F1L is a caspase-9 inhibitor,” Journal of Biological Chemistry, vol. 285, no. 8, pp. 5569–5580, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Aoyagi, D. Zhai, C. Jin et al., “Vaccinia virus N1L protein resembles a B cell lymphoma-2 (Bcl-2) family protein,” Protein Science, vol. 16, no. 1, pp. 118–124, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. C. Gubser, D. Bergamaschi, M. Hollinshead, X. Lu, F. J. van Kuppeveld, and G. L. Smith, “A new inhibitor of apoptosis from vaccinia virus and eukaryotes,” PLoS Pathogens, vol. 3, no. 2, article e17, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. P. Zhang, J. O. Langland, B. L. Jacobs, and C. E. Samuel, “Protein kinase PKR-dependent activation of mitogen-activated protein kinases occurs through mitochondrial adapter IPS-1 and is antagonized by vaccinia virus E3L,” Journal of Virology, vol. 83, no. 11, pp. 5718–5725, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. T. G. Senkevich, E. V. Koonin, and R. M. L. Buller, “A poxvirus protein with a RING zinc finger motif is of crucial importance for virulence,” Virology, vol. 198, no. 2, pp. 118–128, 1994. View at Scopus
  99. T. G. Senkevich, E. J. Wolffe, and R. M. L. Buller, “Ectromelia virus RING finger protein is localized in virus factories and is required for virus replication in macrophages,” Journal of Virology, vol. 69, no. 7, pp. 4103–4111, 1995. View at Scopus
  100. J. Huang, Q. Huang, X. Zhou et al., “The poxvirus p28 virulence factor is an E3 ubiquitin ligase,” Journal of Biological Chemistry, vol. 279, no. 52, pp. 54110–54116, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. C. E. Samuel, “Antiviral actions of interferon interferon-regulated cellular proteins and their surprisingly selective antiviral activities,” Virology, vol. 183, no. 1, pp. 1–11, 1991. View at Publisher · View at Google Scholar · View at Scopus
  102. N. L. Varich, I. V. Sychova, and N. V. Kaverin, “Transcription of both DNA strands of vaccinia virus genome in vivo,” Virology, vol. 96, no. 2, pp. 412–420, 1979. View at Publisher · View at Google Scholar · View at Scopus
  103. P. Whitaker-Dowling and J. S. Youngner, “Characterization of a specific kinase inhibitory factor produced by vaccinia virus which inhibits the interferon-induced protein kinase,” Virology, vol. 137, no. 1, pp. 171–181, 1984. View at Scopus
  104. J. C. Watson, H. W. Chang, and B. L. Jacobs, “Characterization of a vaccinia virus-encoded double-stranded RNA-binding protein that may be involved in inhibition of the double-stranded RNA-dependent protein kinase,” Virology, vol. 185, no. 1, pp. 206–216, 1991. View at Publisher · View at Google Scholar · View at Scopus
  105. M. V. Davies, H. W. Chang, B. L. Jacobs, and R. J. Kaufman, “The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms,” Journal of Virology, vol. 67, no. 3, pp. 1688–1692, 1993. View at Scopus
  106. E. Beattie, J. Tartaglia, and E. Paoletti, “Vaccinia virus-encoded eIF-2α homolog abrogates the antiviral effect of interferon,” Virology, vol. 183, no. 1, pp. 419–422, 1991. View at Publisher · View at Google Scholar · View at Scopus
  107. P. R. Romano, F. Zhang, S. L. Tan et al., “Inhibition of double-stranded RNA-dependent protein kinase PKR by vaccinia virus E3: role of complex formation and the E3 N-terminal domain,” Molecular and Cellular Biology, vol. 18, no. 12, pp. 7304–7316, 1998. View at Scopus
  108. T. A. Brandt and B. L. Jacobs, “Both carboxy- and amino-terminal domains of the vaccinia virus interferon resistance gene, E3L, are required for pathogenesis in a mouse model,” Journal of Virology, vol. 75, no. 2, pp. 850–856, 2001. View at Publisher · View at Google Scholar · View at Scopus
  109. H. W. Chang, J. C. Watson, and B. L. Jacobs, “The E3L gene of vaccinia virus encodes an inhibitor of the interferon- induced, double-stranded RNA-dependent protein kinase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 11, pp. 4825–4829, 1992. View at Publisher · View at Google Scholar · View at Scopus
  110. C. Rivas, J. Gil, Z. Mělková, M. Esteban, and M. Díaz-Guerra, “Vaccinia virus E3L protein is an inhibitor of the interferon (IFN)- induced 2-5A synthetase enzyme,” Virology, vol. 243, no. 2, pp. 406–414, 1998. View at Publisher · View at Google Scholar · View at Scopus
  111. S. N. Shchelkunov, A. V. Totmenin, P. F. Safronov et al., “Analysis of the monkeypox virus genome,” Virology, vol. 297, no. 2, pp. 172–194, 2002. View at Publisher · View at Google Scholar · View at Scopus
  112. P. Bandi, N. E. Pagliaccetti, and M. D. Robek, “Inhibition of type III interferon activity by orthopoxvirus immunomodulatory proteins,” Journal of Interferon and Cytokine Research, vol. 30, no. 3, pp. 123–133, 2010. View at Publisher · View at Google Scholar · View at Scopus
  113. B. A. Mann, J. H. Huang, P. Li et al., “Vaccinia virus blocks Stat1-dependent and Stat1-independent gene expression induced by type I and type II interferons,” Journal of Interferon and Cytokine Research, vol. 28, no. 6, pp. 367–380, 2008. View at Publisher · View at Google Scholar · View at Scopus
  114. A. Alcami and G. L. Smith, “Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity,” Journal of Virology, vol. 69, no. 8, pp. 4633–4639, 1995. View at Scopus
  115. J. A. Symons, A. Alcami, and G. L. Smith, “Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity,” Cell, vol. 81, no. 4, pp. 551–560, 1995. View at Scopus
  116. S. N. Shchelkunov, “Immunomodulatory proteins of orthopoxviruses,” Molecular Biology, vol. 37, no. 1, pp. 37–48, 2003. View at Publisher · View at Google Scholar · View at Scopus
  117. M. D. M. F. De Marco, A. Alejo, P. Hudson, I. K. Damon, and A. Alcami, “The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon,” The FASEB Journal, vol. 24, no. 5, pp. 1479–1488, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. K. J. Tracey and A. Cerami, “Tumor necrosis factor: a pleiotropic cytokine and therapeutic target,” Annual Review of Medicine, vol. 45, pp. 491–503, 1994. View at Publisher · View at Google Scholar · View at Scopus
  119. G. J. Kotwal, “Microorganisms and their interaction with the immune system,” Journal of Leukocyte Biology, vol. 62, no. 4, pp. 415–429, 1997. View at Scopus
  120. G. J. Kotwal, R. Blasco, C. G. Miller, S. Kuntz, S. Jayaraman, and S. N. Shchelkunov, “Strategies for immunomodulation and evasion by microbes: important consideration in the development of live vaccines,” in Symposium in Immunology VII, M. M. Eibl and C. Huber, Eds., pp. 25–47, Springer, Berlin, Germany, 1998.
  121. A. Alcami and U. H. Koszinowski, “Viral mechanisms of immune evasion,” Immunology Today, vol. 21, no. 9, pp. 447–455, 2000. View at Publisher · View at Google Scholar · View at Scopus
  122. G. J. Palumbo, D. J. Pickup, T. N. Fredrickson, L. J. McIntyre, and R. M. L. Buller, “Inhibition of an inflammatory response is mediated by a 38-kDa protein of cowpox virus,” Virology, vol. 172, no. 1, pp. 262–273, 1989. View at Scopus
  123. G. J. Palumbo, W. C. Glasgow, and R. M. L. Buller, “Poxvirus-induced alteration of arachidonate metabolism,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 5, pp. 2020–2024, 1993. View at Scopus
  124. A. Alcami and G. L. Smith, “A soluble receptor for interleukin-1β encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection,” Cell, vol. 71, no. 1, pp. 153–167, 1992. View at Publisher · View at Google Scholar · View at Scopus
  125. A. Alcamí and G. L. Smith, “A mechanism for the inhibition of fever by a virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 20, pp. 11029–11034, 1996. View at Publisher · View at Google Scholar · View at Scopus
  126. T. L. Born, L. A. Morrison, D. J. Esteban et al., “A poxvirus protein that binds to and inactivates IL-18, and inhibits NK cell response,” Journal of Immunology, vol. 164, no. 6, pp. 3246–3254, 2000. View at Scopus
  127. S. N. Shchelkunov, V. M. Blinov, and L. S. Sandakhchiev, “Genes of variola and vaccinia viruses necessary to overcome the host protective mechanisms,” FEBS Letters, vol. 319, no. 1-2, pp. 80–83, 1993. View at Publisher · View at Google Scholar · View at Scopus
  128. C. Upton, J. L. Macen, M. Schreiber, and G. McFadden, “Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence,” Virology, vol. 184, no. 1, pp. 370–382, 1991. View at Scopus
  129. C. A. Smith, F. Q. Hu, T. Davis Smith et al., “Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LTα,” Virology, vol. 223, no. 1, pp. 132–147, 1996. View at Publisher · View at Google Scholar · View at Scopus
  130. V. N. Loparev, J. M. Parsons, J. C. Knight et al., “A third distinct tumor necrosis factor receptor of orthopoxviruses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 7, pp. 3786–3791, 1998. View at Publisher · View at Google Scholar · View at Scopus
  131. A. Saraiva and A. Alcami, “CrmE, a novel soluble tumor necrosis factor receptor encoded by poxviruses,” Journal of Virology, vol. 75, no. 1, pp. 226–233, 2001. View at Publisher · View at Google Scholar · View at Scopus
  132. I. P. Gileva, I. A. Ryazankin, Z. A. Maksyutov et al., “Comparative assessment of the properties of orthopoxviral soluble receptors for tumor necrosis factor,” Doklady Biochemistry and Biophysics, vol. 390, pp. 160–164, 2003. View at Publisher · View at Google Scholar · View at Scopus
  133. I. P. Gileva, T. S. Nepomnyashchikh, D. V. Antonets et al., “Properties of the recombinant TNF-binding proteins from variola, monkeypox, and cowpox viruses are different,” Biochimica et Biophysica Acta, vol. 1764, no. 11, pp. 1710–1718, 2006. View at Publisher · View at Google Scholar · View at Scopus
  134. A. Alejo, M. B. Ruiz-Argüello, Y. Ho, V. P. Smith, M. Saraiva, and A. Alcami, “A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 15, pp. 5995–6000, 2006. View at Publisher · View at Google Scholar · View at Scopus
  135. D. V. Antonets, T. S. Nepomnyashchikh, and S. N. Shchelkunov, “SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family,” BMC Research Notes, vol. 3, article e271, 2010. View at Publisher · View at Google Scholar · View at Scopus
  136. B. J. Rollins, “Chemokines,” Blood, vol. 90, no. 3, pp. 909–928, 1997. View at Scopus
  137. A. H. Patel, D. F. Gaffney, J. H. Subak-Sharpe, and N. D. Stow, “DNA sequence of the gene encoding a major secreted protein of vaccinia virus, strain Lister,” Journal of General Virology, vol. 71, no. 9, pp. 2013–2021, 1990. View at Scopus
  138. C. A. Smith, T. D. Smith, P. J. Smolak et al., “Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits P chemokine activity yet lacks sequence homology to known chemokine receptors,” Virology, vol. 236, no. 2, pp. 316–327, 1997. View at Publisher · View at Google Scholar · View at Scopus
  139. M. W. Bahar, J. C. Kenyon, M. M. Putz et al., “Structure and function of A41, a vaccinia virus chemokine binding protein,” PLoS Pathogens, vol. 4, no. 1, article e5, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. M. B. Ruiz-Argüello, V. P. Smith, G. S. V. Campanella et al., “An ectromelia virus protein that interacts with chemokines through their glycosaminoglycan binding domain,” Journal of Virology, vol. 82, no. 2, pp. 917–926, 2008. View at Publisher · View at Google Scholar · View at Scopus
  141. S. V. Seregin, I. N. Babkina, A. E. Nesterov, A. N. Sinyakov, and S. N. Shchelkunov, “Comparative studies of gamma-interferon receptor-like proteins of variola major and variola minor viruses,” FEBS Letters, vol. 382, no. 1-2, pp. 79–83, 1996. View at Publisher · View at Google Scholar · View at Scopus
  142. C. Upton, K. Mossman, and G. McFadden, “Encoding of a homolog of the IFN-γ receptor by myxoma virus,” Science, vol. 258, no. 5086, pp. 1369–1372, 1992. View at Scopus
  143. K. Mossman, C. Upton, R. M. L. Buller, and G. McFadden, “Species specificity of ectromelia virus and vaccinia virus interferon-γ binding proteins,” Virology, vol. 208, no. 2, pp. 762–769, 1995. View at Publisher · View at Google Scholar · View at Scopus
  144. S. S. Marennikova and S. N. Shchelkunov, Orthopoxviruses Pathogenic for Humans, KMK Press, Moscow, Russia, 1998.
  145. G. J. Kotwal and B. Moss, “Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins,” Nature, vol. 335, no. 6186, pp. 176–178, 1988. View at Scopus
  146. M. K. Liszewski and J. P. Atkinson, “Novel complement inhibitors,” Expert Opinion on Investigational Drugs, vol. 7, no. 3, pp. 323–331, 1998. View at Publisher · View at Google Scholar · View at Scopus
  147. M. D. Kirkitadze, C. Henderson, N. C. Price et al., “Central modules of the vaccinia virus complement control protein are not in extensive contact,” Biochemical Journal, vol. 344, no. 1, pp. 167–175, 1999. View at Publisher · View at Google Scholar · View at Scopus
  148. S. A. Smith, N. P. Mullin, J. Parkinson et al., “Conserved surface-exposed K/R-X-K/R motifs and net positive charge on poxvirus complement control proteins serve as putative heparin binding sites and contribute to inhibition of molecular interactions with human endothelial cells: a novel mechanism for evasion of host defense,” Journal of Virology, vol. 74, no. 12, pp. 5659–5666, 2000. View at Publisher · View at Google Scholar · View at Scopus
  149. C. G. Miller, S. N. Shchelkunov, and G. J. Kotwal, “The cowpox virus-encoded homolog of the vaccinia virus complement control protein is an inflammation modulatory protein,” Virology, vol. 229, no. 1, pp. 126–133, 1997. View at Publisher · View at Google Scholar · View at Scopus
  150. J. Howard, D. E. Justus, A. V. Totmenin, S. Shchelkunov, and G. J. Kotwal, “Molecular mimicry of the inflammation modulatory proteins (IMPS) of poxviruses: evasion of the inflammatory response to preserve viral habitat,” Journal of Leukocyte Biology, vol. 64, no. 1, pp. 68–71, 1998. View at Scopus
  151. E. A. Uvarova and S. N. Shchelkunov, “Species-specific differences in the structure of orthopoxvirus complement-binding protein,” Virus Research, vol. 81, no. 1-2, pp. 39–45, 2001. View at Publisher · View at Google Scholar · View at Scopus
  152. A. M. Rosengard, Y. Liu, Z. Nie, and R. Jimenez, “Variola virus immune evasion design: expression of a highly efficient inhibitor of human complement,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 13, pp. 8808–8813, 2002. View at Publisher · View at Google Scholar · View at Scopus
  153. S. Jonjic, M. Babic, B. Polic, and A. Krmpotic, “Immune evasion of natural killer cells by viruses,” Current Opinion in Immunology, vol. 20, no. 1, pp. 30–38, 2008. View at Publisher · View at Google Scholar
  154. R. M. L. Buller and G. J. Palumbo, “Poxvirus pathogenesis,” Microbiological Reviews, vol. 55, no. 1, pp. 80–122, 1991. View at Scopus
  155. J. A. Campbell, D. S. Trossman, W. M. Yokoyama, and L. N. Carayannopoulos, “Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D,” Journal of Experimental Medicine, vol. 204, no. 6, pp. 1311–1317, 2007. View at Publisher · View at Google Scholar · View at Scopus
  156. H. Okamura, H. Tsutsui, S. I. Kashiwamura, T. Yoshimoto, and K. Nakanishi, “Interleukin-18: a novel cytokine that augments both innate and acquired immunity,” Advances in Immunology, vol. 70, pp. 281–312, 1998. View at Scopus
  157. M. K. Spriggs, “One step ahead of the game: viral immunomodulatory molecules,” Annual Review of Immunology, vol. 14, pp. 101–130, 1996. View at Publisher · View at Google Scholar · View at Scopus
  158. W. E. Demkowicz and F. A. Ennis, “Vaccinia virus-specific CD8+ cytotoxic T lymphocytes in humans,” Journal of Virology, vol. 67, no. 3, pp. 1538–1544, 1993. View at Scopus
  159. K. E. Rehm, R. F. Connor, G. J. B. Jones, K. Yimbu, M. D. Mannie, and R. L. Roper, “Vaccinia virus decreases major histocompatibility complex (MHC) class II antigen presentation, T-cell priming, and peptide association with MHC class II,” Immunology, vol. 128, no. 3, pp. 381–392, 2009. View at Publisher · View at Google Scholar · View at Scopus
  160. K. E. Rehm, R. F. Connor, G. J. B. Jones, K. Yimbu, and R. L. Roper, “Vaccinia virus A35R inhibits MHC class II antigen presentation,” Virology, vol. 397, no. 1, pp. 176–186, 2010. View at Publisher · View at Google Scholar · View at Scopus
  161. K. E. Rehm and R. L. Roper, “Deletion of the A35 gene from modified vaccinia virus Ankara increases immunogenicity and isotype switching,” Vaccine, vol. 29, no. 17, pp. 3276–3283, 2011. View at Publisher · View at Google Scholar · View at Scopus
  162. M. Byun, M. C. Verweij, D. J. Pickup, E. J. H. J. Wiertz, T. H. Hansen, and W. M. Yokoyama, “Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells,” Cell Host and Microbe, vol. 6, no. 5, pp. 422–432, 2009. View at Publisher · View at Google Scholar · View at Scopus
  163. A. Dasgupta, E. Hammarlund, M. K. Slifka, and K. Früh, “Cowpox virus evades CTL recognition and inhibits the intracellular transport of MHC class I molecules,” Journal of Immunology, vol. 178, no. 3, pp. 1654–1661, 2007. View at Scopus
  164. P. M. Murphy, “Molecular mimicry and the generation of host defense protein diversity,” Cell, vol. 72, no. 6, pp. 823–826, 1993. View at Publisher · View at Google Scholar · View at Scopus
  165. B. Beutler and C. van Huffel, “An evolutionary and functional approach to the TNF receptor/ligand family,” Annals of the New York Academy of Sciences, vol. 730, pp. 118–133, 1994. View at Scopus
  166. S. N. Shchelkunov, R. F. Massung, and J. J. Esposito, “Comparison of the genome DNA sequences of Bangladesh-1975 and India-1967 variola viruses,” Virus Research, vol. 36, no. 1, pp. 107–118, 1995. View at Publisher · View at Google Scholar · View at Scopus
  167. R. F. Massung, V. N. Loparev, J. C. Knight et al., “Terminal region sequence variations in variola virus DNA,” Virology, vol. 221, no. 2, pp. 291–300, 1996. View at Publisher · View at Google Scholar · View at Scopus
  168. S. N. Shchelkunov, A. V. Totmenin, V. N. Loparev et al., “Alastrim smallpox variola minor virus genome DNA sequences,” Virology, vol. 266, no. 2, pp. 361–386, 2000. View at Publisher · View at Google Scholar · View at Scopus
  169. S. N. Shchelkunov and A. V. Totmenin, “Two types of deletions in orthopoxvirus genomes,” Virus Genes, vol. 9, no. 3, pp. 231–245, 1995. View at Publisher · View at Google Scholar · View at Scopus