The degree of variability in the amino terminal region of the E2/NS1 protein of hepatitis C virus correlates with responsiveness to interferon therapy in viremic patients.
We investigated amino acid heterogeneity in the variable regions of the E2/NS1 viral protein in interferon-responsive and interferon-nonresponsive patients with chronic hepatitis C virus infection. The study assessed whether any particular heterogeneity pattern(s) could be useful in predicting responsiveness to interferon treatment. The nucleic acid sequences of the hepatitis C virus genome were analyzed from six patients with chronic hepatitis treated with an interferon-beta, three of whom did not respond to the therapy and another three who showed remarkable improvement in the serum levels of liver enzymes and hepatitis C virus RNA after 6 mo. The complementary DNA clones propagated from each of the nonresponders showed significant diversity of both nucleotide and amino acid sequence, especially at the hypervariable region 1 within the putative E2/NS1 gene of the virus, suggesting that these patients were infected with a large heterogeneous pool of hepatitis C virus variants. In contrast, the responders showed little or no diversity in the sequence of the complementary DNA clones, suggesting that they were infected with one or a small population of viral genotypes containing significantly less variability in the E2/NS1 hypervariable region 1. These results suggested that a large variable population of hepatitis C virus genotypes is implicated in patients who are nonresponders to interferon treatment. In addition, a significant change in the hepatitis C virus genotype population was observed in nonresponders after interferon treatment. This may reflect a differential viral sensitivity to interferon, selective immune pressure by the host or both.
Okada
S
S
First Department of Internal Medicine, Yamanashi Medical College, Japan.
Akahane
Y
Y
Suzuki
H
H
Okamoto
H
H
Mishiro
S
S
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000737:chemistry*; D005260:Female; D016174:Hepacivirus / Q000737:chemistry*; D006526:Hepatitis C / Q000097:blood / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D014758:Viral Core Proteins / Q000737:chemistry*
D004279:DNA, Viral; D012367:RNA, Viral; D014758:Viral Core Proteins; D007372:Interferons