Variability of hepatitis C virus

Abstract

The discovery and characterization of the main causative agent of non-A, non-B hepatitis (NANBH) represent a major success in the application of cloning techniques in the identification of new infectious agents.’ The technique that led to the characterization and the development of antibody tests for hepatitis C virus (HCV12 has since been applied successfully to determine the etiological agent of other diseases, such as hepatitis E virus, responsible for enterically transmitted NANBH.3 HCV contains a positive sense RNA genome approximately 10,000 bases in length. In overall genome organization and presumed method of replication, it is most similar to members of the flauiviridae family particularly in the coding for a single polyprotein that is then cleaved into a series of structural proteins (nucleocapsid protein, two membrane glycoproteins) and nonstructural proteins, with presumed enzymatic roles in virus replication. Without a cell culture system to investigate differences in neutralization and cytopathic properties of HCV, nucleotide sequence comparisons and typing assays developed from sequence data have become the principal techniques for characterizing different variants of HCV. This type of analysis is relatively easy to perform, especially because viral sequences can be amplified by the polymerase chain reaction (PCR) directly from clinical specimens. Sequence comparisons of HCV have provided information about the virus a t several levels. It is possible to identify and classify HCV into a series of distinct “genotypes,” which differ substantially in nucleotide sequence from one another and show varied geographical and epidemiological distributions. In particular, the inferred amino acid sequences of the envelope glycoproteins differ considerably, and it is likely that antibody elicited by infection with one genotype would fail to neutralize others. The extent of variation observed within HCV is comparable with that between serotypes of other RNA viruses, and may pose problems in the development of vaccines for HCV.