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You have erased from the calendar of human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed.

—Thomas Jefferson, Letter to Edward Jenner, 1806

Poxviruses belong to Poxviridae family that are the largest and most complex viruses infecting humans, other mammals, birds, and even insects. Poxviruses that infect vertebrates are classified into eight genera, and four of these genera cause disease in humans, including Orthopoxvirus, Parapoxvirus, Yantapoxvirus, and Molluscipoxvirus. Orthopoxvirus genus members that cause disease in humans include variola (smallpox), cowpox, vaccinia (strain used for smallpox vaccination), and monkeypox viruses. Parapoxvirus genus members cause disease mainly in animals but sometimes also in humans, including orf and pseudocowpox viruses. Molluscipoxvirus causes molluscum contagiosum (pearl-like lesions) in humans and Yantapoxvirus comprises tanapox and yabapox viruses that mainly infect animals but may also cause mild disease in humans. The most important agents in human disease are variola (smallpox), vaccinia, monkeypox, molluscum contagiosum, orf, cowpox, and pseudocowpox (Table 11–1). Although smallpox has been eliminated, it has the potential to be used in germ warfare or in bioterrorism. In addition, monkeypox causes similar disease in humans like smallpox but usually milder. Therefore, knowledge and understanding of smallpox pathogenesis and disease are important for any future control of outbreaks of poxviral diseases.

TABLE 11–1Poxviruses (Poxviridae) That Affect Humans


Poxviruses are large, brick-shaped or ovoid, linear double-stranded DNA (130-300 kbp) containing core within a double membrane and a lipoprotein envelope carrying virions measuring approximately 350 × 270 nm (vaccinia virus) (Figures 11–1 and 11–2). The core is flanked by two lateral bodies containing several viral enzymes and proteins, including DNA-dependent RNA polymerase and transcription factors required for viral replication. The poxvirus genome encodes all essential enzymes, proteins, and factors needed for viral replication in the cytoplasm of infected cells, including transcription, DNA synthesis, and virus assembly. The envelope is acquired in the cytoplasm either from the Golgi apparatus or other cellular organelles, but not by budding from the plasma membrane and may not be essential for viral infectivity.

FIGURE 11–1.

Schematic diagram of the structure of poxvirus virion. Viral DNA and several viral proteins within the core form the nucleosome (N). The core is covered with a 9 nm thick core membrane (CM) and assumes a dumbbell ...

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