The Discovery of the Hepatitis C Virus

Abstract

After a 6-year intensive search for the causative agent of parenteral non-A, non-B hepatitis using a large variety of pre-PCR molecular biological, immunological, and virological methods, HCV was discovered using a cDNA immunoscreening method in which infectious chimpanzee plasma was used as the source of cloning material and NANBH patient sera as a presumptive source of NANBH-specific antibodies. Clone 5-1-1 and overlapping clones were shown to be extrachromosomal in origin, to be derived from a large single-stranded RNA found only in NANBH materials and which directly encoded an antigen shown to specifically bind antibodies in most parenteral NANBH-infected chimpanzees and patients. The nucleotide sequence of the RNA genome exhibited low homology with flaviviruses which in combination proved that HCV was the major cause of blood-borne NANBH and that it was a distant relative of the Flaviviridae family. Since 1990, a series of HCV-specific antibody- and RNA-detecting blood screening tests have effectively eliminated posttransfusion HCV infections. Subsequent decades of research by the field into the viral life cycle and the development of direct-acting antivirals have now led to HCV becoming the first curable, chronically infecting virus of man. It is now important to focus on a prophylactic vaccine to curtail this global epidemic.