In vivo replication and reversion to wild type of a neutralization-resistant antigenic variant of hepatitis A virus

Abstract

Six seronegative owl monkeys were intravenously inoculated with an antigenic variant (SI8) of hepatitis A virus that is highly adapted to growth in cell culture and resists neutralization by monoclonal antibodies due to replacement of aspartic acid 70 of capsid protein VP3 with histidine. Each developed hepatitis 2233 days after inoculation. Virus in feces, serum, and liver was quantified by radioimmunofocus assay. Viremia developed 711 days after inoculation, in parallel with fecal shedding of virus, and persisted for a mean of 20.5 days. Although the antigenic variant was recovered from feces or liver of three animals, virus in liver at the time of enzyme elevations was predominantly wild-type antigenic phenotype. Virus was not recoveredfrom liver 96 days after challenge. These studies further define virologic events in hepatitis A and show that in vivo replication of an antigenic variant was restricted compared with that of wildtype virus. © 1990 by The University of Chicago. All rights reserved.