Viral Hepatitis
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 28, 2007; 13(8): 1195-1203
Published online Feb 28, 2007. doi: 10.3748/wjg.v13.i8.1195
Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy
Pascal Veillon, Christopher Payan, Hélène Le Guillou-Guillemette, Catherine Gaudy, Françoise Lunel
Pascal Veillon, Hélène Le Guillou-Guillemette, Françoise Lunel, Laboratory of Virology, Angers University Hospital, 4 rue Larrey, 49933 Angers cedex 9, France
Christopher Payan, Departement of Microbiology, EA 3882, Brest University Hospital, 2 avenue Foch, 29609 Brest cedex, France
Catherine Gaudy, University Francois Rabelais, INSERM ERI 19, Faculty of Medecine, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex, France
Pascal Veillon, Hélène Le Guillou-Guillemette, Françoise Lunel, HIFIH Laboratory, UPRES EA 3859, IFR 132, University of Angers, rue de Haute Reculée, 49045 Angers, France
Author contributions: All authors contributed equally to the work.
Supported by a grant from l’Agence National de la Recherche sur le Sida (ANRS grant 2001/011)
Correspondence to: Professor Françoise Lunel, Service de Bactériologie-Virologie et Hygiène Hospitalière, CHU ANGERS, 4 rue Larrey; 49933 ANGERS cedex 9, France. frlunel-fabiani@chu-angers.fr
Telephone: +33-2-41355493 Fax: +33-2-41354164
Received: September 26, 2006
Revised: October 25, 2006
Accepted: December 9, 2006
Published online: February 28, 2007
Abstract

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 cloning 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 combined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their response to the treatments: 7 with sustained virological response (SVR) (quasispecies = 150) and 3 non-responders (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 quasispecies during therapy. Analysis of amino acids substitutions 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 the two groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients.

CONCLUSION: These results suggest that detailed molecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.

Keywords: Hepatitis C virus; Quasispecies; NS5A region; Interferon sensitivity-determining region; V3 domain