title: Identification of VP1/2A and 2C as virulence genes of hepatitis A virus and demonstration of genetic instability of 2C.
abstract: Fourteen different chimeric virus genomes were constructed from two infectious cDNA clones encoding a virulent and an attenuated isolate, respectively, of the HM175 strain of hepatitis A virus. The ability of each recombinant virus to infect tamarins and to cause acute hepatitis was determined. Comparisons of the genotype and phenotype of each virus suggested that VP1/2A and 2C genes were responsible for virulence. The 2C gene derived from the attenuated parent virus was unstable, and one or more mutations arose in this gene during the first passage in tamarins.
authors.affiliation: Molecular Hepatitis. Hepatitis Viruses Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8009, USA. semerson@niaid.nih.gov
authors.forename: Suzanne U
authors.initials: SU
authors.lastname: Emerson
authors.forename: Ying K
authors.initials: YK
authors.lastname: Huang
authors.forename: Hanh
authors.initials: H
authors.lastname: Nguyen
authors.forename: Alicia
authors.initials: A
authors.lastname: Brockington
authors.forename: Sugantha
authors.initials: S
authors.lastname: Govindarajan
authors.forename: Marisa
authors.initials: M
authors.lastname: St  Claire
authors.forename: Max
authors.initials: M
authors.lastname: Shapiro
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006506:Hepatitis A / Q000503:physiopathology / Q000821:virology; D030041:Hepatitis A virus / Q000235:genetics / Q000472:pathogenicity*; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic; D012452:Saguinus; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins; D015678:Viral Structural Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C096539:VP1 protein, hepatitis A virus; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus; C076023:2C protein, viral