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

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 × 10⁴ 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 of6 animals and peak viremia and fecal shedding ofvirus occurred 18 or 19 days after intravenous inoculation of about one-tenth as much virus.