Smallpox virus

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This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Smallpox.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]


Smallpox is caused by the variola virus, a dsDNA virus of the Poxviridae family. There are two forms of this virus with different virulences, as evidenced by their respective death rates. The virus survives in the cold and aerosoled environments, which explains its oral transmission among humans. Humans are the viruses only host which likely facilitated its eradication. Unlike other DNA viruses, smallpox replicates within the cytoplasm, to which it shows tropism.


Viruses; dsDNA; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Variola vera


Variola virus, also known as smallpox virus, is an orthopoxvirus, from the family Poxviridae, the largest viruses to infect humans. It is a 200-400 nm dsDNA virus, lacking icosahedral symmetry. The other viruses of the family Poxviridae include:[1]

The viral structure includes:[2][3][4]

Variola virus genes are similar to the ones of vaccinia virus. Since there is cross-protection between poxviruses, it was possible to use the second as a vaccine for smallpox virus.[5]

There are 2 forms of variola virus:

  • Variola major
  • Variola minor

Both strains of the virus share a large amount of genome, yet they differ clinically. This leads to the assumption that the difference in virulence resides in alternate gene expression.[1][6]

Poxviruses survive in cold and dry environments being able to survive in the aerosoled form, and are killed by hospital disinfectants and UV light.[1][6][7][8]

Unlike other DNA viruses, poxviruses replicate within the cytoplasm of the host cell. In order to replicate, poxviruses produce a variety of specialized proteins, not produced by other DNA viruses, the most important of which is a viral-associated DNA-dependent RNA polymerase.


The date of the origin of the smallpox virus is not settled. It most likely evolved from a rodent virus between 68,000 and 16,000 years ago.[9][10] This broad range of dates is due to the different records used to calibrate the molecular clock. It appears that the smallpox virus derived from a remote zoonosis from another animal host, that is today extinct.[11]


Little is known about the mechanism responsible for host species tropism of smallpox virus. The virus is known to bind mammalian cells unspecifically. There appears to be no particular extracellular receptors involved in viral internalization and initial transcription. However, intracellular availability of trans-acting factors and viral capacity to block host cells antiviral response, such as the interferon pathway, are though to be important intracellular factors, determining viral tropism. The overall immune response by the host towards the virus, will be the key determinant of the infection's outcome and potential transmission to other hosts.[11]

Natural reservoir

Humans are the only known natural reservoir of the smallpox virus.[12]


  1. 1.0 1.1 1.2 Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.
  2. Fields, Bernard (2007). Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 0781760607.
  3. Massung RF, Liu LI, Qi J, Knight JC, Yuran TE, Kerlavage AR; et al. (1994). "Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975". Virology. 201 (2): 215–40. doi:10.1006/viro.1994.1288. PMID 8184534.
  4. Massung RF, Loparev VN, Knight JC, Totmenin AV, Chizhikov VE, Parsons JM; et al. (1996). "Terminal region sequence variations in variola virus DNA". Virology. 221 (2): 291–300. doi:10.1006/viro.1996.0378. PMID 8661439.
  5. Shchelkunov, Sergei N.; Resenchuk, Sergei M.; Totmenin, Alexei V.; Blinov, Vladimir M.; Marennikova, Svetlana S.; Sandakhchiev, Lev S. (1993). "Comparison of the genetic maps of variola and vaccinia viruses". FEBS Letters. 327 (3): 321–324. doi:10.1016/0014-5793(93)81013-P. ISSN 0014-5793.
  6. 6.0 6.1 "Smallpox and its Eradication" (PDF).
  7. Thomas G (1974). "Air sampling of smallpox virus". J Hyg (Lond). 73 (1): 1–7. PMC 2130554. PMID 4371586.
  8. HARPER GJ (1961). "Airborne micro-organisms: survival tests with four viruses". J Hyg (Lond). 59: 479–86. PMC 2134455. PMID 13904777.
  9. Esposito, J. J. (2006). "Genome Sequence Diversity and Clues to the Evolution of Variola (Smallpox) Virus". Science. 313 (5788): 807–812. doi:10.1126/science.1125134. ISSN 0036-8075.
  10. 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". Proceedings of the National Academy of Sciences. 104 (40): 15787–15792. doi:10.1073/pnas.0609268104. ISSN 0027-8424.
  11. 11.0 11.1 McFadden, Grant (2005). "Poxvirus tropism". Nature Reviews Microbiology. 3 (3): 201–213. doi:10.1038/nrmicro1099. ISSN 1740-1526.
  12. "Smallpox disease overview".

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