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

• Published in: The Journal of infectious diseases Vol. 168; no. 3; pp. 592 - 601
• Main Authors: Taylor, Kerry L., Murphy, Paula C., Asher, Ludmila V. S., LeDuc, James W., Lemon, Stanley M.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.09.1993; University of Chicago Press
• Subjects: Adaptation, Biological; Alanine Transaminase - blood; Animals; Antibodies; Antibody Formation; Aotidae; Biological and medical sciences; Biopsies; Cell culture techniques; Cultured cells; Disease Susceptibility; Female; gamma-Glutamyltransferase - blood; Genetic Variation; Hepatitis A - genetics; Hepatitis A - immunology; Hepatitis A - veterinary; Hepatitis A virus; Hepatovirus - growth & development; Hepatovirus - isolation & purification; Hepatovirus - pathogenicity; Human viral diseases; Infectious diseases; Inoculation; Liver; Liver - pathology; Liver - ultrastructure; Major Articles; Male; Medical sciences; Mutation; Phenotype; Phenotypes; Serial Passage; Splenectomy; Time Factors; Viral diseases; Viral hepatitis; Viremia; Virulence; Virus Shedding; Viruses; Cell culture; Hepatitis A virus; Intravenous administration; Picornaviridae; Viremia; Genetic variant; Virulence; Monkey; Hepatic disease; Infection; Virus; Pathogenicity; Viral hepatitis A; Vertebrata; Experimental disease; Phenotype; Mammalia; Viral disease; Animal; Primates; Digestive diseases; Mutation; Attenuated strain
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/168.3.592

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.