Descartes before the horse: I clone, therefore I am: the hepatitis C virus in current perspective.

Abstract

In an unprecedented approach to viral discovery, the hepatitis C virus (HCV) was cloned before it was established by conventional methods of viral detection or by genomic characterization. Hepatitis C virus is a small (10-kb), single-stranded RNA virus with a genomic organization that places it in the family Flaviviridae. The virus is global in distribution, with a prevalence between 0.3% and 1.5%. The same agent causes parenterally acquired and sporadic non-A, non-B hepatitis. Nonparenteral modes of spread are poorly defined, but low-level sexual transmission is probable. There is a strong association between the presence of antibody to HCV (anti-HCV) and hepatocellular carcinoma; a causal role for HCV is suspected but has not been proved. Hepatitis C virus accounts for at least 85% of the cases of transfusion-associated hepatitis; an anti-HCV-reactive donor was retrospectively identified in nearly 90% of cases. Among donors confirmed by recombinant immunoblot assay (RIBA) to be anti-HCV positive, 80% to 90% are infectious. Hepatitis C virus RNA can be detected within 1 to 2 weeks of exposure and persists throughout the course of infection. Generally, the presence of anti-HCV cannot be confirmed until 9 to 20 weeks after exposure, creating a window period of seronegativity and potential infectivity. It is anticipated that the anti-HCV assay will reduce the number of cases of transfusion-associated hepatitis by 50% in the United States; a 70% reduction has been documented in Spain.