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World J Gastroenterol. May 7, 2007; 13(17): 2416-2426
Published online May 7, 2007. doi: 10.3748/wjg.v13.i17.2416
Genetic diversity of the hepatitis C virus: Impact and issues in the antiviral therapy
H Le Guillou-Guillemette, S Vallet, C Gaudy-Graffin, C Payan, A Pivert, A Goudeau, F Lunel-Fabiani
H Le Guillou-Guillemette, F Lunel-Fabiani, A Pivert, Laboratory of Virology, University Hospital of Angers, France and Laboratory HIFI, UPRES EA 3859, University of Angers, France
S Vallet, C Payan, Department of Microbiology, EA 3882, CHU Morvan, University Hospital of Brest, France
C Gaudy-Graffin, A Goudeau, Université François Rabelais, INSERM ERI 19 et CHRU de Tours, Tours, France
Author contributions: All authors contributed equally to the work.
Correspondence to: F Lunel-Fabiani, Professor, Laboratory of Virology, Department of infectious agents, University Hospital of Angers, 4 rue Larrey, 49933 Angers Cedex 9,France.
Telephone: +33-2-41354709 Fax: +33-2-41354164
Received: December 23, 2006
Revised: December 28, 2006
Accepted: March 13, 2007
Published online: May 7, 2007

The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The resulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the predictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic success. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antiviral therapy in patients infected by the same HCV genotype. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Interferon pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity. Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non-structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

Keywords: Hepatitis C virus, Genetic diversity, Therapy resistance, E2, NS3, NS5A, NS5B