Attenuation Phenotype of a Cell Culture-Adapted Variant of Hepatitis A Virus (HM175/p16) in Susceptible New World Owl Monkeys

J Infect Dis. 1993 Sep;168(3):592-601. doi: 10.1093/infdis/168.3.592.

Abstract

The virulence of a clonally isolated, cell culture-adapted hepatitis A virus (HM175/p16) was assessed in 4 seronegative owl monkeys inoculated intravenously with 2.8 x 10(4) radioimmunofocus-forming units of virus. The virus was highly attenuated, even though its complete nucleotide sequence contains only 19 mutations from the wild-type genome. Only 3 monkeys developed antibodies to hepatitis A virus (only 2 within 96 days of virus inoculation). One monkey had viremia and significantly elevated serum aminotransferase levels. In this animal, maximum viremia and fecal shedding of virus occurred 30-33 days after inoculation. In contrast, in earlier studies of a related cell culture-adapted but still hepatovirulent virus (HM175/S18), viremia was documented in 6 of 6 animals and peak viremia and fecal shedding of virus occurred 18 or 19 days after intravenous inoculation of about one-tenth as much virus.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Biological*
  • Alanine Transaminase / blood
  • Animals
  • Antibody Formation
  • Aotidae
  • Disease Susceptibility
  • Female
  • Genetic Variation
  • Hepatitis A / genetics
  • Hepatitis A / immunology
  • Hepatitis A / veterinary*
  • Hepatovirus / growth & development
  • Hepatovirus / isolation & purification
  • Hepatovirus / pathogenicity*
  • Liver / pathology
  • Liver / ultrastructure
  • Male
  • Mutation
  • Phenotype
  • Serial Passage
  • Splenectomy
  • Time Factors
  • Viremia
  • Virulence
  • Virus Shedding
  • gamma-Glutamyltransferase / blood

Substances

  • gamma-Glutamyltransferase
  • Alanine Transaminase