Mechanisms of HCV survival in the host

HCV infection is a key cause of liver disease and a worldwide health problem. The authors of this Review discuss the HCV life cycle and the mechanisms that enable the virus to evade host immune mechanisms and persist within the host. Improved understanding of HCV survival strategies should facilitate the development of effective antiviral therapies. HCV infection is an important cause of liver disease worldwide—nearly 80% of infected patients develop chronic liver disease, which leads to the development of liver cirrhosis and hepatocellular carcinoma. The ability of HCV to persist within a host is believed to be related to the numerous mechanisms by which it evades the immune response of the host. These mechanisms can be divided into defensive and offensive strategies. Examples of defensive mechanisms include replication within enclosed structures, which provides protection from the host's antiviral defenses, genetic diversity created by inaccurate replication, which yields mutants resistant to the cell's antiviral strategies, and association of the virion with protective lipoproteins. Offensive mechanisms include virally encoded proteins and other factors that disrupt the ability of the host cells to detect the virus and downregulate its ability to respond to interferon, impair innate immune defense mechanisms and alter T-cell responses, and prevent the development of an effective B-cell-mediated humoral response. Greater understanding of these viral survival strategies will ultimately translate into more effective antiviral therapies and better prognosis for patients.