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Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

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World Journal of Gastroenterology 2007年第8期13卷 1195-1203页

作者： Pascal Veillon Christopher Payan Hélène Le Guillou-Guillemette catherine gaudy Franoise Lunel Laboratory of Virology Angers University Hospital 4 rue Larrey 49933 Angers cedex 9 France HIFIH Laboratory UPRES EA 3859 IFR 132 University of Angers rue de Haute Reculée 49045 Angers France Departement of Microbiology EA 3882 Brest University Hospital 2 avenue Foch 29609 Brest cedex France University Francois Rabelais INSERM ERI 19 Faculty of Medecine 10 Boulevard Tonnellé BP 3223 37032 Tours Cedex France

AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.

关键词： Hepatitis C virus Quasispecies NS5A region Interferon sensitivity-determining region V3 domain

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