Molecular biology of hepatitis A virus: significance of various substitutions in the hepatitis A virus genome

Abstract

Hepatitis A virus (HAV) is the sole member of the hepatogenus of Picorna viridae. This virus can now be propagated in cell culture and in primates. Molecular biological studies of HAV have disclosed its genomic structure and the functional significance of the viral proteins to some extent. Hepatitis A virus has a positive-stranded RNA of approximately 7.5 kb that encodes a large polyprotein. Translation of the protein is influenced by the function of the internal ribosomal entry site in the 5' non-translating region. It is generally agreed that the polyprotein is processed to four structural and seven non-structural proteins by the proteinase encoded in the 3C region. Replication efficiency seems to be controlled by amino acid substitutions in the 2B and 2C regions. The virulence of HAV in primates may be determined by substitutions in the 2C region. Although the severity of hepatitis A was thought to be determined by immunological reactions of the host to the virus, the potential virulence of the variant viruses themselves may need further examination. Recent progress in polymerase chain reaction technology has made possible an analysis of the HAV sequence in clinical specimens; such analysis is of importance in the disclosure of differences in HAV subspecies in different clinical conditions.