Live Variola Virus Considerations for Continuing Research (2009) / Chapter Skim
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4 Animal Models Using Variola and Other Orthopoxviruses
4 Animal Models Using Variola and Other Orthopoxviruses
Pages 49-58
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offers some features that are suggestive of later-stage, fulminant human smallpox, the ability of this model system to mimic the wide spectrum of human disease manifestations and pathophysiology remains uncertain. This chapter describes efforts to use animal models to study variola infection and disease in humans.
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Of note, the reports described primary and secondary viremias and a mild, brief illness with fever and rash in Macaca irus and Macaca mulatta exposed to variola virus via the aerosol route (Hahon and Wilson, 1960; Lancaster et al., 1966; Westwood et al., 1966)
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Vaccinia, cowpox, and mousepox Vaccinia virus is perhaps the most widely used poxvirus in animal m odels for studying variola virus infection because of its ready availability and extensive knowledge base, and the susceptibility of laboratory rabbits and mice to vaccinia infection. In rabbits in particular, infection with a r abbit-adapted strain of vaccinia virus -- rabbitpox virus -- generates a disease that recapitulates some of the important features of smallpox, including transmission between hosts by the aerosol route and a generalized rash (Adams et al., 2007)
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However, the ability to perform challenge experiments with vaccinia, cowpox, and mousepox viruses in a single species when protection against all three viruses can be achieved with traditional smallpox vaccine adds considerably to the confidence with which extrapolations from these models to human smallpox can be made. Monkeypox Monkeypox is perhaps the most relevant orthopoxvirus with regard to nonvariola animal models for smallpox.
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ChimerIC Viruses While the extreme host restriction of variola virus greatly facilitated the smallpox eradication campaign, it also hampered research because no animal model using variola was available. In the 1960s, attempts were made to address this gap by constructing chimeric viruses from variola and either cowpox or rabbitpox (a rabbit-adapted strain of vaccinia virus)
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and vaccinia produces disease with features that mimic human smallpox. bDisseminated vaccinia infection in humans produces disease with some features reminiscent of smallpox.
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2007. Rabbitpox virus and vaccinia virus infection of rabbits as a model for human smallpox.
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2003. Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates.
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2004. Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge.
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