title: Molecular basis of virulence and growth of hepatitis A virus in cell culture.
abstract: The ability of engineering variants of hepatitis A virus (strain HM175) to replicate in cell culture or to cause disease in marmosets was evaluated. Virus variants were encoded by chimeric genomes constructed from infectious cDNA clones of two viruses (wild type and cell-culture-adapted) which differed in their ability to grow in vitro and to cause acute hepatitis in marmosets. Transfection and infectivity assays indicated that virus growth in vitro could be enhanced by subcloning the cell substrate prior to infection or by introducing multiple combinations of two or more mutations into the wild type genome. Various chimeric viruses induced liver enzyme elevations in marmosets, indicating that attenuation of virulence also required multiple mutations.
authors.affiliation: Hepatitis Virus Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: S U
authors.initials: SU
authors.lastname: Emerson
authors.forename: Y K
authors.initials: YK
authors.lastname: Huang
authors.forename: C
authors.initials: C
authors.lastname: McRill
authors.forename: M
authors.initials: M
authors.lastname: Lewis
authors.forename: M
authors.initials: M
authors.lastname: Shapiro
authors.forename: W T
authors.initials: WT
authors.lastname: London
authors.forename: R H
authors.initials: RH
authors.lastname: Purcell
mesh_terms: D000818:Animals; D002144:Callithrix / Q000382:microbiology; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics*; D005814:Genes, Viral; D006506:Hepatitis A / Q000382:microbiology*; D006507:Hepatovirus / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D009154:Mutation; D014162:Transfection; D014774:Virulence / Q000235:genetics; D014776:Virus Cultivation; D014779:Virus Replication
chemical_list: D004279:DNA, Viral