The prognosis of Hepatitis B and C virus (HBV, HCV) infected patients is influenced by multiple factors, among which viral mutations and its nature of quasispecies can be closely related to all aspects of the disease progress of these patients, including chroni-calization, acute flares of chronic hepatitis, and the emerging of severe hepatitis as well as cirrhosis and hepatocellular carcinoma (2, 3, 4, 5).
It has been well stated that in any single host, HBV and HCV exist as closely related yet genetically distinguished variants known as quasispecies, based on the lack of proofreading of their polymerases (6). Variants possess the highest fitness to environment may exist as predominant quasispecies while others remain as minor variants. The proportion of these variants may fluctuate according to environmental changes so that to keep the whole population fit best to the changing circumstances. By these means, the quasispecies nature of HBV and HCV has endowed these hypervariable viruses competences of recrui-ting numerous variants to compete with any environ-mental pressures the population might encounter with. By sacrificing non-vital variants, reserving less-fit yet potential variants, and dominating one or several highest fit variant (s), a reservoir of various variants was generated which may possess a strong com-petence of adapting to and evolving with the changing environments (7, 11). Therefore, when facing with host immune pressure or antiviral drugs, potential fitful variants which may previously be minor quasi-species can be selected and accumulate to be dominant quasispecies. The quasispecies nature may be one of the main reasons for immune escape and drug resistance of these hypervariable viruses.
The Role of Viral Mutation in the Pathogenesis of Chronic Viral Hepatitis
- Received Date: 24 December 2007
- Accepted Date: 24 January 2008
Abstract: The quasispecies nature of hepatitis B and C virus (HBV, HCV) plays an important role in the pathogenesis, immune escape and drug resistance during chronic infection. Although there is still a lack of effective treatment for hepatitis C, a series of nucleoside analogs (NA) have been developed for the treatment of hepatitis B. NA resistant HBV mutants can accumulate during prolonged therapy and lead to the failure of anti-HBV therapy. Switching to other sensitive NAs can inhibit the emerged resistant mutants. Therefore, understanding the evolution of viral quasispecies under drug pressure is crucial for the establishment of antiviral strategy and the monitoring of antiviral process. Immune response and escape are complicated process, during which both host and virus factors may play their roles. Further understanding of the interaction and interrelationship between host and these viruses may lead to optimized prevention, diagnosis and treatment for chronic hepatitis.