Skip to main content

Genus Orthopoxvirus: Variola virus

  • Chapter
Book cover Poxviruses

Part of the book series: Birkhäuser Advances in Infectious Diseases ((BAID))

Abstract

Variola major virus caused the human disease smallpox; interpretations of the historic record indicate that the initial introduction of disease in a naïve population had profound effects on its demographics. Smallpox was declared eradicated by the World Health Organization (WHO) in 1980. This chapter reviews epidemiological, clinical and pathophysiological observations of disease, and review some of the more recent observations on the microbiology of Variola virus

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Esposito JJ, Sammons SA, Frace AM, Osborne JD, Olsen-Rasmussen M, Zhang M, Govil D, Damon IK, Kline R, Laker M et al (2006) Genome sequence diversity and clues to the evolution of Variola virus.Science 313: 807–812

    Article  PubMed  Google Scholar 

  2. Gubser C, Smith GL (2002) The sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox. J Gen Virol 83: 855–872

    PubMed  CAS  Google Scholar 

  3. Dixon CW (1962) Smallpox. J.& A. Churchill, London

    Google Scholar 

  4. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID (1988) Smallpox and its Eradication. World Health Organization, Geneva

    Google Scholar 

  5. Henderson DA, Moss B (1999) Smallpox and Vaccinia. In: S Plotkin, W Orenstein (eds): Vaccines. Saunders, New York, 74–97

    Google Scholar 

  6. Creighton C (1894) History of Epidemics in Britain. Cambridge University Press, London

    Google Scholar 

  7. Jenner E (1798) An enquiry into the causes and effects of variolae vaccinae, a disease discovered in some of the western couties of England, particularly Gloucerstershire, and known by the name of cowpox. Samson Low, London

    Google Scholar 

  8. Jenner E (1799) Further observations on the variolae vaccinae. Samson Low, London

    Google Scholar 

  9. Franco-Paredes C, Lammoglia L, Santos-Preciado JI (2005) The Spanish royal philanthropic expedition to bring smallpox vaccination to the New World and Asia in the 19th century. Clin Infect Dis 41: 1285–1289

    Article  PubMed  Google Scholar 

  10. Baxby D (1999) The orgins of vaccinia virus-an even shorter rejoinder. Soc Hist Med 12: 139

    Article  PubMed  CAS  Google Scholar 

  11. Baxby D (1999) Edward Jenner’s Inquiry; a bicentenary analysis. Vaccine 17: 301–307

    Article  PubMed  CAS  Google Scholar 

  12. Collier LH (1954) The preservation of vaccinia virus. Bacteriol Rev 18: 74–86

    PubMed  CAS  Google Scholar 

  13. National Research Council (1999) Assessment of Future Needs for Live Variola Virus. NAS Press, Washington, D.C.

    Google Scholar 

  14. Leduc JW, Damon I, Relman DA, Huggins J, Jahrling PB (2002) Smallpox research activities: U.S. interagency collaboration, 2001. Emerg Infect Dis 8: 743–745

    PubMed  Google Scholar 

  15. Leduc JW, Jahrling PB (2001) Strengthening national preparedness for smallpox: an update. Emerg Infect Dis 7: 155–157

    Article  PubMed  CAS  Google Scholar 

  16. Noble J Jr, Rich JA (1969) Transmission of smallpox by contact and by aerosol routes in Macaca irus. Bull World Health Organ 40: 279–286

    PubMed  Google Scholar 

  17. Kalter SS, Rodriguez AR, Cummins LB, Heberling RL, Foster SO (1979) Experimental smallpox in chimpanzees. Bull World Health Organ 57: 637–641

    PubMed  CAS  Google Scholar 

  18. Heberling RL, Kalter SS, Rodriguez AR (1976) Poxvirus infection of the baboon (Papio cynocephalus). Bull World Health Organ 54: 285–294

    PubMed  CAS  Google Scholar 

  19. Downie AW, Meiklejohn M, St Vincent L, Rao AR, Sundara Babu BV, Kempe CH (1965) The recovery of smallpox virus from patients and their environment in a smallpox hospital. Bull World Health Organ 33: 615–622

    PubMed  CAS  Google Scholar 

  20. Mack TM, Thomas DB, Muzaffar KM (1972) Epidemiology of smallpox in West Pakistan. II Determinants of intravillage spread other than acquired immunity. Am J Epidemiol 95: 169–177

    PubMed  CAS  Google Scholar 

  21. Mack TM, Thomas DB, Ali A, Muzaffar KM (1972) Epidemiology of smallpox in West Pakistan. I.Acquired immunity and the distribution of disease. Am J Epidemiol95: 157–168

    CAS  Google Scholar 

  22. Heiner GG, Fatima N, McCrumb FR Jr (1971) A study of intrafamilial transmission of smallpox. Am J Epidemiol 94: 316–326

    PubMed  CAS  Google Scholar 

  23. Rao AR, Jacob ES, Kamalakshi S, Appaswamy S, Bradbury (1968) Epidemiological studies in smallpox. A study of intrafamilial transmission in a series of 254 infected families. Indian J Med Res 56: 1826–1854

    PubMed  CAS  Google Scholar 

  24. Mack TM (1972) Smallpox in Europe, 1950-1971. J Infect Dis 125: 161–169

    PubMed  CAS  Google Scholar 

  25. Wehrle PF, Posch J, Richter KH, Henderson DA (1970) An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe. Bull World Health Organ 43: 669–679

    PubMed  CAS  Google Scholar 

  26. Stallybrass CO (1931) The principles of epidemiology and the process of infection. Routledge, London, 329

    Google Scholar 

  27. Thomas DB, McCormack WM, Arita I, Khan MM, Islam S, Mack TM (1971) Endemic smallpox in rural East Pakistan. I.Methodology, clinical and epide miologic characteristics of cases, and intervillage transmission. Am J Epidemiol 93: 361–372

    CAS  Google Scholar 

  28. Arita I, Wickett JF, Fenner F (1986) Impact of population density on immunization programs. J Hyg Camb 96: 459–466

    PubMed  CAS  Google Scholar 

  29. Duncan SR, Scott S, Duncan CJ (1993) An hypothesis for the periodicity of smallpox epidemics as revealed by time series analysis. J Theor Biol 160: 231–248

    Article  PubMed  CAS  Google Scholar 

  30. Rao AR (1972) Smallpox. The Kothari Book Depot, Bombay

    Google Scholar 

  31. Rao AR, Prahlad I, Swaminathan M, Lakshmi A (1963) Pregnancy and smallpox. J Indian Med Assoc 40: 353–363

    PubMed  CAS  Google Scholar 

  32. Harper GJ (1961) Airborne micro-organisms: survival tests with four viruses. J Hyg (Lond) 59: 479–486

    CAS  Google Scholar 

  33. Kitamura T, Aoyama Y, Kurata T, Arita M, Imagawa Y (1977) Virological studies of smallpox in an endemic area. II. Virus content of clinical specimens and typing of virus isolates. Jpn J Med Sci Biol 30: 229–239

    PubMed  CAS  Google Scholar 

  34. Sarkar JK, Mitra AC, Mukherjee MK, De SK, Mazumdar DG (1973) Virus excretion in smallpox. 1._Excretion in the throat, urine, and conjunctiva of patients. Bull World Health Organ 48: 517–522

    CAS  Google Scholar 

  35. Downie AW, St Vincent L, Meiklejohn G, Ratnakannan NR, Rao AR, Krishnan GN, Kempe CH (1961) Studies on the virus content of mouth washings in the acute phase of smallpox. Bull World Health Organ 25: 49–53

    PubMed  CAS  Google Scholar 

  36. Downie AW, Fedson DS, Saint VL, Rao AR, Kempe CH (1969) Haemorrhagic smallpox. J Hyg (Lond) 67: 619–629

    CAS  Google Scholar 

  37. Sarkar JK, Mitra AC, Chakravarty MS (1972) Relationship of clinical severity, antibody level, and previous vaccination state in smallpox. Trans R Soc Trop Med Hyg 66: 789–792

    Article  PubMed  CAS  Google Scholar 

  38. Rao AR (1964) Haemorrhagic smallpox: a study of 240 cases. J Indian Med Assoc 43: 224–229

    PubMed  CAS  Google Scholar 

  39. Rao AR, Sukumar MS, Kamalakshi S, Paramasivam TV, Parasuraman TA, Shantha M (1968) Experimental variola in monkeys. I.Studies on disease enhancing property of cortisone in smallpox. A preliminary report. Indian J Med Res 56: 1855–1865

    CAS  Google Scholar 

  40. Downie AW, McCarthy K, Macdonald A, Maccallum FO, Macrae AE (1953) Virus and virus antigen in the blood of smallpox patients; their significance in early diagnosis and prognosis. Lancet 265: 164–166

    Article  PubMed  CAS  Google Scholar 

  41. Downie AW, McCarthy K, Macdonald A (1950) Viraemia in smallpox. Lancet 2: 513–514

    Article  PubMed  CAS  Google Scholar 

  42. Downie AW, Fedson DS, Saint VL, Rao AR, Kempe CH (1969) Haemorrhagic smallpox. J Hyg (Lond) 67: 619–629

    CAS  Google Scholar 

  43. Jahrling PB, Hensley LE, Martinez MJ, Leduc JW, Rubins KH, Relman DA, Huggins JW (2004) Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox. Proc Natl Acad Sci USA 101: 15196–15200

    Article  PubMed  CAS  Google Scholar 

  44. Rubins KH, Hensley LE, Jahrling PB, Whitney AR, Geisbert TW, Huggins JW, Owen A, Leduc JW, Brown PO, Relman DA (2004) The host response to smallpox: analysis of the gene expression program in peripheral blood cells in a nonhuman primate model. Proc Natl Acad Sci USA 101: 15190–15195

    Article  PubMed  CAS  Google Scholar 

  45. Bras G (1952) The morbid anatomy of smallpox. Doc Med Geogr Trop 4: 303

    PubMed  CAS  Google Scholar 

  46. Marennikova S, Maltseva MN, Korneeva VI, Garanina NM (1977) Pox outbreak among carnivora (Felidae) and Endentata. J Infect Dis 135: 358

    PubMed  CAS  Google Scholar 

  47. Greene HSN (1934) Rabbitpox. II. Pathology of the epidemic disease. J Exp Med 60: 427

    Google Scholar 

  48. Smith GL (1993) Vaccinia virus glycoproteins and immune evasion. The sixteenth Fleming Lecture. J Gen Virol 74: 1725–1740

    Article  PubMed  CAS  Google Scholar 

  49. Shchelkunov SN (1995) Functional organization of variola major and vaccinia virus genomes. Virus Genes 10: 53–71

    Article  PubMed  CAS  Google Scholar 

  50. Massung RF, Esposito JJ, Liu LI, Qi J, Utterback TR, Knight JC, Aubin L, Yuran TE, Parsons JM, Loparev VN et al (1993) Potential virulence determinants in terminal regions of variola smallpox virus genome. Nature 366: 748–751

    Article  PubMed  CAS  Google Scholar 

  51. Senkevich TG, Koonin EV, Buller RM (1994) A poxvirus protein with a RING zinc finger motif is of crucial importance for virulence. Virology 198: 118–128

    Article  PubMed  CAS  Google Scholar 

  52. Shchelkunov SN, Resenchuk SM, Totmenin AV, Blinov VM, Marennikova SS, Sandakhchiev LS (1993) Comparison of the genetic maps of variola and vaccinia viruses. FEBS Lett 327: 321–324

    Article  PubMed  CAS  Google Scholar 

  53. Alcami A, Smith GL (1993) Comment on the paper by Shchelkunov et al (1993) FEBS Letters 319, 80–83. Two genes encoding poxvirus cytokine receptors are disrupted or deleted in variola virus. FEBS Lett 335: 136–137

    Article  Google Scholar 

  54. Buller RM, Palumbo GJ (1991) Poxvirus pathogenesis. Microbiol Rev 55: 80–122

    PubMed  CAS  Google Scholar 

  55. Chen N, Li G, Liszewski MK, Atkinson JP, Jahrling PB, Feng Z, Schriewer J, Buck C, Wang C, Lefkowitz EJ et al (2005) Virulence differences between monkeypox virus isolates from West Africa and the Congo basin. Virology 340: 46–63

    Article  PubMed  CAS  Google Scholar 

  56. McFadden G (2005) Poxvirus tropism. Nat Rev Microbiol 3: 201–213

    Article  PubMed  CAS  Google Scholar 

  57. Jahrling PB, Fritz EA, Hensley LE (2005) Countermeasures to the bioterrorist threat of smallpox. Curr Mol Med 5: 817–826

    Article  PubMed  CAS  Google Scholar 

  58. Massung RF, Loparev VN, Knight JC, Totmenin AV, Chizhikov VE, Parsons JM, Safronov PF, Gutorov VV, Shchelkunov SN, Esposito JJ (1996) Terminal region sequence variations in variola virus DNA. Virology 221: 291–300

    Article  PubMed  CAS  Google Scholar 

  59. Dunlop LR, Oehlberg KA, Reid JJ, Avci D, Rosengard AM (2003) Variola virus immune evasion proteins. Microbes Infect 5: 1049–1056

    Article  PubMed  CAS  Google Scholar 

  60. Esteban DJ, Buller RM (2005) Ectromelia virus: the causative agent of mousepox. J Gen Virol 86: 2645–2659

    Article  PubMed  CAS  Google Scholar 

  61. Barry M, McFadden G (1997) Virus encoded cytokines and cytokine receptors. Parasitology 115 Suppl: S89–100

    Article  Google Scholar 

  62. Cao JX, McFadden G (2001) Characterization of the myxoma virus M118L protein: a novel essential poxvirus IMV-associated protein. Virus Genes 23: 303–313

    Article  PubMed  CAS  Google Scholar 

  63. Everett H, McFadden G (2002) Poxviruses and apoptosis: a time to die. Curr Opin Microbiol 5: 395–402

    Article  PubMed  CAS  Google Scholar 

  64. Johnston JB, McFadden G (2004) Technical knockout: understanding poxvirus pathogenesis by selectively deleting viral immunomodulatory genes. Cell Microbiol 6: 695–705

    Article  PubMed  CAS  Google Scholar 

  65. Johnston JB, McFadden G (2003) Poxvirus immunomodulatory strategies: current perspectives. J Virol 77: 6093–6100

    Article  PubMed  CAS  Google Scholar 

  66. Lalani AS, Masters J, Zeng W, Barrett J, Pannu R, Everett H, Arendt CW, McFadden G (1999) Use of chemokine receptors by poxviruses. Science 286: 1968–1971

    Article  PubMed  CAS  Google Scholar 

  67. Smith CA, Smith TD, Smolak PJ, Friend D, Hagen H, Gerhart M, Park L, Pickup DJ, Torrance D, Mohler K et al (1997) Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology 236: 316–327

    Article  PubMed  CAS  Google Scholar 

  68. Rosengard AM, Liu Y, Nie Z, Jimenez R (2002) Variola virus immune evasion design: expression of a highly efficient inhibitor of human complement. Proc Natl Acad Sci USA 99: 8808–8813

    PubMed  CAS  Google Scholar 

  69. Rosengard AM, Alonso LC, Korb LC, Baldwin WM III, Sanfilippo F, Turka LA, Ahearn JM (1999) Functional characterization of soluble and membrane-bound forms of vaccinia virus complement control protein (VCP). Mol Immunol 36: 685–697

    Article  PubMed  CAS  Google Scholar 

  70. Isaacs SN, Kotwal GJ, Moss B (1992) Vaccinia virus complement-control protein prevents antibody-dependent complement-enhanced neutralization of infectivity and contributes to virulence. Proc Natl Acad Sci USA 89: 628–632

    Article  PubMed  CAS  Google Scholar 

  71. Kotwal GJ, Isaacs SN, McKenzie R, Frank MM, Moss B (1990) Inhibition of the complement cascade by the major secretory protein of vaccinia virus. Science 250: 827–830

    Article  PubMed  CAS  Google Scholar 

  72. Sfyroera G, Katragadda M, Morikis D, Isaacs SN, Lambris JD (2005) Electrostatic modeling predicts the activities of orthopoxvirus complement control proteins. J Immunol 174: 2143–2151

    PubMed  CAS  Google Scholar 

  73. Buller RM, Chakrabarti S, Moss B, Fredrickson T (1988) Cell proliferative response to vaccinia virus is mediated by VGF. Virology 164: 182–192

    Article  PubMed  CAS  Google Scholar 

  74. Buller RM, Chakrabarti S, Cooper JA, Twardzik DR, Moss B (1988) Deletion of the vaccinia virus growth factor gene reduces virus virulence. J Virol 62: 866–874

    PubMed  CAS  Google Scholar 

  75. Kim M, Yang H, Kim SK, Reche PA, Tirabassi RS, Hussey RE, Chishti Y, Rheinwald JG, Morehead TJ, Zech T et al (2004) Biochemical and functional analysis of smallpox growth factor (SPGF) and anti-SPGF monoclonal antibodies. J Biol Chem 279: 25838–25848

    Article  PubMed  CAS  Google Scholar 

  76. Born TL, Morrison LA, Esteban DJ, VandenBos T, Thebeau LG, Chen N, Spriggs MK, Sims JE, Buller RM (2000) A poxvirus protein that binds to and inactivates IL-18, and inhibits NK cell response. J Immunol 164: 3246–3254

    PubMed  CAS  Google Scholar 

  77. Symons JA, Adams E, Tscharke DC, Reading PC, Waldmann H, Smith GL (2002) The vaccinia virus C12L protein inhibits mouse IL-18 and promotes virus virulence in the murine intranasal model. J Gen Virol 83: 2833–2844

    PubMed  CAS  Google Scholar 

  78. Reading PC, Smith GL (2003) Vaccinia virus interleukin-18-binding protein promotes virulence by reducing gamma interferon production and natural killer and T-cell activity. J Virol 77: 9960–9968

    Article  PubMed  CAS  Google Scholar 

  79. Esteban DJ, Nuara AA, Buller RM (2004) Interleukin-18_and glycosaminoglycan binding by a protein encoded by Variola virus. J Gen Virol 85: 1291–1299

    Article  PubMed  CAS  Google Scholar 

  80. Alejo A, Ruiz-Arguello MB, Ho Y, Smith VP, Saraiva M, Alcami A (2006) A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus. Proc Natl Acad Sci USA 103: 5995–6000

    Article  PubMed  CAS  Google Scholar 

  81. Huang J, Huang Q, Zhou X, Shen MM, Yen A, Yu SX, Dong G, Qu K, Huang P, Anderson EM et al (2004) The poxvirus p28 virulence factor is an E3 ubiquitin ligase. J Biol Chem 279: 54110–54116

    Article  PubMed  CAS  Google Scholar 

  82. Senkevich TG, Wolffe EJ, Buller RM (1995) Ectromelia virus RING finger protein is localized in virus factories and is required for virus replication in macrophages. J Virol 69: 4103–4111

    PubMed  CAS  Google Scholar 

  83. Brick DJ, Burke RD, Minkley AA, Upton C (2000) Ectromelia virus virulence factor p28 acts upstream of caspase-3 in response to UV light-induced apoptosis. J Gen Virol 81: 1087–1097

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Damon, I.K. (2007). Genus Orthopoxvirus: Variola virus . In: Mercer, A.A., Schmidt, A., Weber, O. (eds) Poxviruses. Birkhäuser Advances in Infectious Diseases. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7557-7_2

Download citation

Publish with us

Policies and ethics