The prognostic relevance of the nonstructural 5A gene interferon sensitivity determining region is different in infections with genotype 1b and 3a isolates of hepatitis C virus.
Hepatitis C virus (HCV) RNA serum concentration, quasispecies complexity, and sequence and phylogenetic analysis of the nonstructural 5A gene (NS5A) interferon sensitivity determining region (ISDR) were determined in pretreatment serum samples from 47 patients with chronic hepatitis C (36 infected by HCV genotype 1b and 11 by 3a). Among HCV genotype 1b-infected patients, virus load was lower (P = .003) and the number of NS5A-ISDR amino acid changes was higher (P = .001) in long-term responders than in non-long-term responders, but there were no differences in quasispecies complexity. Multivariate analysis showed a close association between response to interferon and NS5A-ISDR phenotype. Phylogenetic analysis showed that isolates from non-long-term responders clustered apart from the majority of isolates from long-term responders. There was no association between virologic features and therapeutic response in HCV genotype 3a-infected patients. In conclusion, low virus load and mutant NS5A-ISDR phenotype are closely associated with long-term response to interferon in HCV genotype 1b- but probably not in 3a-infected patients.
Sáiz
J C
JC
Hospital Clinic, Department of Medicine, Facultad de Medicina, Universidad de Barcelona, Spain. JCSAIZ@medicina.ub.es
López-Labrador
F X
FX
Ampurdanés
S
S
Dopazo
J
J
Forns
X
X
Sánchez-Tapias
J M
JM
Rodés
J
J
D000328:Adult; D000595:Amino Acid Sequence; D002908:Chronic Disease; D018076:DNA, Complementary / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D018076:DNA, Complementary; D007370:Interferon Type I; D012367:RNA, Viral; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase