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Chapter 33 : Hepatitis A Virus Pathogenesis and Attenuation

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Abstract:

In 1973, Feinstone and coworkers first visualized hepatitis A virus (HAV) in the feces of an individual with acute hepatitis A. HAV was originally classified as enterovirus 72, but subsequent analysis of the sequence of its genome in comparison with newer information about the genomic sequences of other picornaviruses led to its being reclassified in its own genus, Hepatovirus, which it shares with the closely related simian HAVs. The current hypothesis is that viral hepatitis is both caused and cured by the cytotoxic T lymphocyte (CTL) activity of CD8 lymphocytes infiltrating the virus-infected liver. In general, wild-type strains of HAV recovered from clinical cases of acute hepatitis replicate extremely slowly and to low titer in vitro and inoculated cell cultures may require months of incubation before maximum amounts of virus are produced. Coincident with this adaptation to cell culture, the virus, in some cases, lost its virulence for primates or humans and acquired an attenuation phenotype. As hepatitis A vaccines are based on the immunogenicity of intact virions, an appreciation of the molecular basis for efficient growth in cell culture or of attenuation has been necessary for the development of such vaccines. Live attenuated hepatitis A vaccines also have been developed by isolation and blind serial passage in cells. The most promising candidate vaccines have been grown in primary or continuous monkey kidney cells. However, virtually all primary monkey kidney cells are contaminated with simian viruses and therefore not useful for vaccine propagation.

Citation: Purcell R, Emerson S. 2002. Hepatitis A Virus Pathogenesis and Attenuation, p 415-425. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch33

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Inactivated Hepatitis A Vaccine
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FIGURE 1

Clinical, virologie, and serologic events in a typical case of hepatitis A, as observed in experimentally infected nonhuman primates and confirmed by natural and experimental infections of humans.

Citation: Purcell R, Emerson S. 2002. Hepatitis A Virus Pathogenesis and Attenuation, p 415-425. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch33
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Tables

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TABLE 1

Relative susceptibility of chimpanzees and tamarins to oral versus intravenous inoculation with hepatitis A virus

Citation: Purcell R, Emerson S. 2002. Hepatitis A Virus Pathogenesis and Attenuation, p 415-425. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch33

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