1887

Abstract

Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to ∼40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.

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2009-04-01
2024-04-16
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References

  1. Aldaz-Carroll L., Whitbeck J. C., Ponce de Leon M., Lou H., Hirao L., Isaacs S. N., Moss B., Eisenberg R. J., Cohen G. H. 2005; Epitope-mapping studies define two major neutralization sites on the vaccinia virus extracellular enveloped virus glycoprotein B5R. J Virol 79:6260–6271 [CrossRef]
    [Google Scholar]
  2. Appleyard G., Hapel A. J., Boulter E. A. 1971; An antigenic difference between intracellular and extracellular rabbitpox virus. J Gen Virol 13:9–17 [CrossRef]
    [Google Scholar]
  3. Bell E., Shamim M., Whitbeck J. C., Sfyroera G., Lambris J. D., Isaacs S. N. 2004; Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin. Virology 325:425–431 [CrossRef]
    [Google Scholar]
  4. Blasco R., Moss B. 1992; Role of cell-associated enveloped vaccinia virus in cell-to-cell spread. J Virol 66:4170–4179
    [Google Scholar]
  5. Davies D. H., Molina D. M., Wrammert J., Miller J., Hirst S., Mu Y., Pablo J., Unal B., Nakajima-Sasaki R. other authors 2007; Proteome-wide analysis of the serological response to vaccinia and smallpox. Proteomics 7:1678–1686 [CrossRef]
    [Google Scholar]
  6. Engelstad M., Smith G. L. 1993; The vaccinia virus 42-kDa envelope protein is required for the envelopment and egress of extracellular virus and for virus virulence. Virology 194:627–637 [CrossRef]
    [Google Scholar]
  7. Engelstad M., Howard S. T., Smith G. L. 1992; A constitutively expressed vaccinia gene encodes a 42-kDa glycoprotein related to complement control factors that forms part of the extracellular virus envelope. Virology 188:801–810 [CrossRef]
    [Google Scholar]
  8. Esposito J. J., Sammons S. A., Frace A. M., Osborne J. D., Olsen-Rasmussen M., Zhang M., Govil D., Damon I. K., Kline R. other authors 2006; Genome sequence diversity and clues to the evolution of variola (smallpox) virus. Science 313:807–812 [CrossRef]
    [Google Scholar]
  9. Gurt I., Abdalrhman I., Katz E. 2006; Pathogenicity and immunogenicity in mice of vaccinia viruses mutated in the viral envelope proteins A33R and B5R. Antiviral Res 69:158–164 [CrossRef]
    [Google Scholar]
  10. Herrero-Martínez E., Roberts K. L., Hollinshead M., Smith G. L. 2005; Vaccinia virus intracellular enveloped virions move to the cell periphery on microtubules in the absence of the A36R protein. J Gen Virol 86:2961–2968 [CrossRef]
    [Google Scholar]
  11. Katz E., Wolffe E., Moss B. 2002; Identification of second-site mutations that enhance release and spread of vaccinia virus. J Virol 76:11637–11644 [CrossRef]
    [Google Scholar]
  12. Katz E., Ward B. M., Weisberg A. S., Moss B. 2003; Mutations in the vaccinia virus A33R and B5R envelope proteins that enhance release of extracellular virions and eliminate formation of actin-containing microvilli without preventing tyrosine phosphorylation of the A36R protein. J Virol 77:12266–12275 [CrossRef]
    [Google Scholar]
  13. Li Y., Carroll D. S., Gardner S. N., Walsh M. C., Vitalis E. A., Damon I. K. 2007; On the origin of smallpox: correlating variola phylogenics with historical smallpox records. Proc Natl Acad Sci U S A 104:15787–15792 [CrossRef]
    [Google Scholar]
  14. McIntosh A. A. G., Smith G. L. 1996; Vaccinia virus glycoprotein A34R is required for infectivity of extracellular enveloped virus. J Virol 70:272–281
    [Google Scholar]
  15. Parkinson J. E., Smith G. L. 1994; Vaccinia virus gene A36R encodes a M r 43–50 K protein on the surface of extracellular enveloped virus. Virology 204:376–390 [CrossRef]
    [Google Scholar]
  16. Payne L. G. 1980; Significance of extracellular enveloped virus in the in vitro and in vivo dissemination of vaccinia. J Gen Virol 50:89–100 [CrossRef]
    [Google Scholar]
  17. Payne L. G., Kristensson K. 1985; Extracellular release of enveloped vaccinia virus from mouse nasal epithelial cells in vivo . J Gen Virol 66:643–646 [CrossRef]
    [Google Scholar]
  18. Putz M. M., Midgley C. M., Law M., Smith G. L. 2006; Quantification of antibody responses against multiple antigens of the two infectious forms of vaccinia virus provides a benchmark for smallpox vaccination. Nat Med 12:1310–1315 [CrossRef]
    [Google Scholar]
  19. Rotz L. D., Dotson D. A., Damon I. K., Becher J. A. 2001; Vaccinia (smallpox. vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Recomm Rep 501–25
    [Google Scholar]
  20. Sanderson C. M., Frischknecht F., Way M., Hollinshead M., Smith G. L. 1998; Roles of vaccinia virus EEV-specific proteins in intracellular actin tail formation and low pH-induced cell–cell fusion. J Gen Virol 79:1415–1425
    [Google Scholar]
  21. Shida H. 1986; Variants of vaccinia virus hemagglutinin altered in intracellular transport. Mol Cell Biol 6:3734–3745
    [Google Scholar]
  22. Smith G. L., Vanderplasschen A., Law M. 2002; The formation and function of extracellular enveloped vaccinia virus. J Gen Virol 83:2915–2931
    [Google Scholar]
  23. Stanford M. M., McFadden G., Karupiah G., Chaudhri G. 2007; Immunopathogenesis of poxvirus infections: forecasting the impending storm. Immunol Cell Biol 85:93–102 [CrossRef]
    [Google Scholar]
  24. Trindade G. S., Emerson G. L., Carroll D. S., Kroon E. G., Damon I. K. 2007; Brazilian vaccinia viruses and their origins. Emerg Infect Dis 13:965–972 [CrossRef]
    [Google Scholar]
  25. Vanderplasschen A., Mathew E., Hollinshead M., Sim R. B., Smith G. L. 1998; Extracellular enveloped vaccinia virus is resistant to complement because of incorporation of host complement control proteins into its envelope. Proc Natl Acad Sci U S A 95:7544–7549 [CrossRef]
    [Google Scholar]
  26. van Eijl H., Hollinshead M., Rodger G., Zhang W. H., Smith G. L. 2002; The vaccinia virus F12L protein is associated with intracellular enveloped virus particles and is required for their egress to the cell surface. J Gen Virol 83:195–207
    [Google Scholar]
  27. Wolffe E. J., Isaacs S. N., Moss B. 1993; Deletion of the vaccinia virus B5R gene encoding a 42-kilodalton membrane glycoprotein inhibits extracellular virus envelope formation and dissemination. J Virol 67:4732–4741
    [Google Scholar]
  28. Yang H., Kim S. K., Kim M., Reche P. A., Morehead T. J., Damon I. K., Welsh R. M., Reinherz E. L. 2005; Antiviral chemotherapy facilitates control of poxvirus infections through inhibition of cellular signal transduction. J Clin Invest 115:379–387 [CrossRef]
    [Google Scholar]
  29. Zhang W. H., Wilcock D., Smith G. L. 2000; Vaccinia virus F12L protein is required for actin tail formation, normal plaque size, and virulence. J Virol 74:11654–11662 [CrossRef]
    [Google Scholar]
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