Variola virus causes the human smallpox (also known as Variola or Variola vara in Latin, and pox or red plague in English), an infectious disease unique to humans. Smallpox is caused by either of two variants of the variola virus: Variola major and Variola minor. The infection of variola virus is focused in small blood vessels of the skin and in the mouth and throat before disseminating. Variola major infection causes a more serious disease with a mortality rate of 30%-35%. Variola minor infection, however, causes a relatively mild form of disease (also known as milkpox, alastrim, whitepox, cottonpox, and Cuban itch) with a mortality rate of only 1%. The smallpox disease was claimed to be eradicated by the WHO in the year 1979, after vaccination campaigns throughout the 19th and 20th centuries.
Variola virus belongs to the family Poxviridae, subfamily chordopoxvirinae and genus Orthopoxvirus. Variola virus particle is a large, brick-shaped with the size of approximately 302 to 350 nanometers by 244 to 270 nm. Genome of variola virus is a single linear, double stranded DNA molecule with a length of about 186kbp. Each terminals of variola genome contains one hairpin loop. The viral genome encodes approximately 200 proteins, and over 80 of them are located in the terminal regions. But only several variola proteins have been characterized up to now, such as the smallpox inhibitor of complement enzymes (SPICE), the e variola virus high-affinity secreted chemokine-binding protein type II(CKBP-II, CBP-II, or vCCI),and the cytokine response modifier B (CRMB).
Fig. 2 Schematic representation of a variola-infected cell and variola-encoded immunomodulators (L.R. Dunlop et al. Microbes and Infection, 2003)
The SPICE protein has been described to be homologous to a vaccinia virus virulence factor called vaccinia virus complement-control protein (VCP). SPICE and VCP are similar not only in structure but also in function to the family of mammalian complement regulatory proteins, whose function is to prevent inadvertent injury to adjacent cells and tissues during complement activation. The CKBP-II proteins bind CC-chemokine receptors and are highly conserved among orthopoxviruses. CRMB protein is the only cytokine response modifier encoded by variola virus. They block the proinflammtatory and antiviral effects of TNF and function as decoy TNF receptors.
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