Biology and genetic heterogeneity of hepatitis C virus

Abstract

Hepatitis C virus (HCV) has a significant, albeit varied, presence around the world. This virus is primarily transmitted parenterally, although sexual and perinatal transmission does appear to occur. However, no risk factor for transmission could be identified in a significant proportion of infected individuals. It was found that individuals became viremic early after the primary HCV infection, whereas seroconversion and hepatitis occurred several weeks later. It was demonstrated that less than 20% of patients cleared their viremia, with the majority of patients becoming chronically infected. A significant proportion of chronically infected individuals developed chronic hepatitis and liver cirrhosis, and a strong association has been found with the development of hepatocellular carcinoma. Finally, HCV seems to be associated with autoimmune diseases and type II cryoglobulinemia. Thus, significant morbidity and mortality is caused by HCV infection worldwide. In a single infected individual the genome population of HCV has been found to comprise a quasispecies that consists of a number of identical sequences (i.e., the master sequence) and other closely related sequences. The master sequence of this quasispecies population changes during infection. In particular, it has been found that the sequence of the hypervariable region I changes rapidly in infected individuals. It is possible that the quasispecies nature of HCV constitutes a mechanism by which HCV escapes immune surveillance and establishes a persistent infection in the host. It is now well established that HCV exists as distinct genotypes among different HCV isolates. According to the currently used classification these can be divided into a number of major genetic groups (or types) and subgroups (or subtypes). The extensive genetic heterogeneity of HCV has important implications for diagnosis, pathogenesis, treatment and vaccine development.