Influence of viral quasispecies on effectiveness of interferon therapy in chronic hepatitis C patients.
The quasispecies nature of hepatitis C virus genome distribution is most evident in hypervariable regions of the putative envelope 2 domain. Eight patients with chronic hepatitis C treated with interferon-alpha were studied as to heterogeneity of the hypervariable regions to clarify the implications of quasispecies. More than 10 recombinant clones generated from polymerase chain reaction-amplified products of the hypervariable regions were sequenced. The sets of clones derived from long-term responders before interferon therapy showed a significantly lower (p < 0.05) degree of sequence complexity of the hypervariable region 1 quasispecies than those from short-term ones or non-responders. The values of nucleotide diversity (the average number of nucleotide differences per site between two randomly chosen sequences) in hypervariable region 1 before interferon therapy were also significantly lower (p < 0.05) for long-term responders (mean, 2.31 x 10(-2)). In some cases, nucleotide diversity decreased remarkably during interferon therapy, whereas the values remained unchanged in other cases. In one interesting case, a short-term response was first noted with the nucleotide diversity decreasing from 13.98 x 10(-2) to 0.21 x 10(-2); namely, the diversity of the quasispecies was significantly reduced, and then a long-term response was observed after an additional course of interferon therapy. Thus, the degree of quasispecies' complexity and diversity of hypervariable region 1 was closely correlated with the responsiveness to interferon therapy in chronic hepatitis C patients, and thus may have some influence on interferon efficacy.
Kanazawa
Y
Y
First Department of Medicine, Osaka University School of Medicine, Japan.
Hayashi
N
N
Mita
E
E
Li
T
T
Hagiwara
H
H
Kasahara
A
A
Fusamoto
H
H
Kamada
T
T
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D001483:Base Sequence; D002908:Chronic Disease; D016679:Genome, Viral; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics
D015345:Oligonucleotide Probes; D007372:Interferons; D000410:Alanine Transaminase