Genetic Diversity and Molecular evolution of Hepatitis C Virus

Hepatitis C virus (HCV), an enveloped positive stranded RNA virus, is the causative agent of non-A, non-B (NANB) hepatitis (27). The virus was identified and characterized by molecular cloning techniques using serum from a NANB hepatitis virus infected chimpanzee (15) and based on the similarity of the genome organization and hydropathy profiles of several precursor proteins classified as a member of the Flaviviridae family. However, the low sequence homology compared to other flaviviruses eventually lead to its classification into a new genus hepacivirus, distinct from the other flavivirus members (33, 74). Initial studies demonstrated that blood transfusions were the main transmission route that caused the HCV epidemic, especially prior to the period of HCV-contaminated blood screening in 1992 (50). HCV high-risk groups include recipients of multiple blood transfusion, hemophiliacs, hemodialysis patients and intravenous drug users. Modes of transmission include contact with contaminated-blood products, sharing needles, mother-to-child and sexual transmissions (69). Infection of the human liver is often clinically benign, with mild symptoms in the acute phase and fulminant hepatitis is very rare. The disease may even go unnoticed in cases of acute resolving HCV. In most cases (>70%) HCV infection leads to chronic persistent or active infection, often accompanied by complications of liver cirrhosis, or type II cryoglobulinaemia. The mechanisms of HCV persistence are not fully understood but the inability of the host innate and specific immune system to clear the virus is remarkable for a positive stranded RNA virus. HCV specific CD8+ T-cell responses are considered to play an important role in the containment and clearance of HCV infection but few of these cells are present in the liver and are unable to eradicate the infection. In addition, antibodies to HCV do not seem to play a major role in clearance of infection and re-infections are often observed with a different HCV strain, suggesting that immune responses to the initial strain did not protect against an infection with another strain of HCV (43).

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