[Mutation analysis of ISDR and V3 domains of hepatitis C virus NS5A region before interferon therapy with or without ribavirin].
OBJECTIVE
The hepatitis C virus (HCV) non-structural NS5A protein has been controversially implicated in the resistance of HCV to interferon therapy in clinical studies. In Japan, mutations in the interferon sensitivity-determining region (ISDR) in the NS5A gene were associated with response to interferon therapy in patients infected with genotype 1b. In contrast, studies from Europe did not confirm such association. More recently, it has been suggested that the V3 domain outside the putative ISDR might also have amino acids changes that may be involved in the resistance to IFN. In this study, the relationship between NS5A mutations in ISDR and V3 domains and virological response to therapy were investigated.


METHODS
The NS5A gene was sequenced from 35 HCV genotype 1b infected patients at D0 of a prospective clinical trial of interferon therapy and interferon plus Ribavirin combination therapy.


RESULTS
In the ISDR domain, we did not observe any significant differences in amino acids changes between responders (1.7 +/- 1.8, n = 19, range 0-6) and non-responders (1.1 +/- 0.8, n = 14, range: 0-3), (P = 0.483), to therapy before the beginning of treatment. In the V3 domain, we found more mutations in responders (6.5 +/- 1.9, range: 2-11) than in non-responders (4.7 +/- 1.2, range: 3-8) (P = 0.0013), before the beginning of treatment.


CONCLUSIONS
Our results confirm that, in Europe, the ISDR domain is not predictive for treatment success but suggest that the V3 domain have greater variability in responders than non-responders.
Veillon
P
P
Laboratoire de bactériologie-virologie et hygiène hospitalière, CHU d'Angers, 4, rue Larrey 49033 Angers, France. pascal_veillon@hotmail.com
Payan
C
C
Gaudy
C
C
Goudeau
A
A
Lunel
F
F
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use; D001483:Base Sequence; D024882:Drug Resistance, Viral; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D012254:Ribavirin / Q000627:therapeutic use*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D007372:Interferons; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase