The hepatitis C virus: overview.

Our knowledge of hepatitis C virus (HCV) dates only from 1975, when non-A, non-B hepatitis was first recognized. It was not until 1989 that the genome of the virus was first cloned and sequenced, and expressed viral antigens used to develop serological assays for screening and diagnosis. HCV is in a separate genus of the virus family Flaviviridae. It is a spherical enveloped virus of approximately 50 nm in diameter. Its genome is a single-stranded linear RNA molecule of positive sense and consists of a 5' noncoding region, a single large open reading frame, and a 3' noncoding region. The open reading frame encodes at least three structural and six nonstructural proteins. The genome is characterized by significant genetic heterogeneity, based on which HCV isolates can be classified into six major genotypes and more than 50 subtypes. Even individual isolates of HCV are genetically heterogeneous (quasispecies diversity). Genetic heterogeneity of HCV is greatest in the amino-terminal end of the second envelope protein (hypervariable region 1). This region may represent a neutralization epitope that is under selective pressure from the host's humoral immune response. Infection with HCV proceeds to chronicity in more than 80% of cases, and even recovery does not protect against subsequent re-exposure to the virus. The development of a broadly protective vaccine against HCV will therefore require a better understanding of the molecular biology and immune response to this virus.