The discovery of hepatitis viruses: Agents & disease

Abstract Discovery of five hepatitis viruses A to E has followed distinctive definable phases. Human experiments at Willowbrook identified two forms of hepatitis namely infectious hepatitis and serum hepatitis. The discovery of Australia antigen in 1965 led to rapid scientific developments in viral hepatitis. SH antigen was detected in sera of patients with serum hepatitis and soon SH antigen & Australia antigen were found to be identical and selectively associated with serum hepatitis. In 1970, 42 nm Dane particles were detected in Australia antigen positive sera and linked to the virus of serum hepatitis. Subsequently, a new antigen-antibody system (e-antigen/antibody) was detected in such patients and associated with infectivity. Next DNA polymerase was found in concentrated pellets containing Australia antigen. HBV DNA cloning and sequencing of HBV followed these developments. In 1973, 27 nm hepatitis A virus like particles were visualized in stool samples obtained during acute phase of illness following inoculation of MS-1 strain in volunteers. Cloning and sequencing of HAV followed. In 1977, a new antigen-antibody system (δ antigen-antibody system) was identified by chance associated with HBV. Based on animal transmission studies, δ agent was found to be another virus (HDV) that is defective, requires the helper functions of HBV and interferes with HBV replication. The search for hepatitis C virus started when non-A, non-B hepatitis was recognised in multiply transfused patients with subsequent successful animal transmission. HCV was identified by a novel immunoscreening approach involving screening of cDNA libraries from infectious sera. The story of hepatitis E is historically linked to discovery of water-borne Epidemic Non-A, Non-B Hepatitis from Kashmir, India. virus-like-particles of the agent were identified in stool samples of a human volunteer following a self-experimentation. HEV cDNA was detected in bile-enriched infectious samples and full-length HEV RNA genome was subsequently cloned and sequenced.