Genetic heterogeneity of the envelope 2 gene and eradication of hepatitis C virus after a second course of interferon-alpha.
The heterogeneity of the envelope 2 (E2) gene of the hepatitis C virus (HCV) was involved in the sensitivity of HCV to interferon-alpha (IFN-alpha). To assess the factors leading to virus eradication by IFN-alpha, patients whose first treatment by IFN-alpha failed and who had virus eradication after a second treatment were studied. These patients were paired with subjects in whom both treatments failed. The phosphorylation homology domain of the E2 gene (E2-PHD) had no sequence variation between the two stages in both groups of patients. Therefore, this region has no clinical predictive value within a specific genotype. The hypervariable region 1 (HVR1) was analyzed by cloning and sequencing 20 clones per sample. Comparison of samples showed that the change in quasispecies induced by the first IFN-alpha therapy could be associated with virus elimination obtained after a second treatment. The greater proportion of nonsynonymous mutations that was noted before the second treatment in responders suggest that pretherapeutic immune response is a major factor determining virus elimination and that the immune status of these patients changed between the first and the second treatment.
Boulestin
Anne
A
Laboratoire de Virologie, Hôpital Purpan, Toulouse Cedex, France. izopet@cict.fr
Sandres-Sauné
Karine
K
Payen
Jean-Louis
JL
Alric
Laurent
L
Dubois
Martine
M
Pasquier
Christophe
C
Vinel
Jean-Pierre
JP
Pascal
Jean-Pierre
JP
Puel
Jacqueline
J
Izopet
Jacques
J
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015752:Genes, env; D014644:Genetic Variation; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins; D012189:Retrospective Studies; D017386:Sequence Homology, Amino Acid; D017211:Treatment Failure; D014759:Viral Envelope Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics
D004279:DNA, Viral; C400562:HVR1 protein, Hepatitis C virus; D007370:Interferon Type I; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C091015:glycoprotein E2, Hepatitis C virus