Genetic changes in the interferon sensitivity determining region of hepatitis C virus during the natural course of chronic hepatitis C.

Abstract

Amino acid mutations in the interferon sensitivity determining region (ISDR) are closely associated with the response to interferon in patients with hepatitis C virus genotype 1b (HCV-1b) infection. In this study, 36 patients chronically infected with HCV-1b, with no history of interferon therapy with respect to ISDR changes in HCV were studied. Two serum samples were obtained from each patient, with an average interval of 3.5 years, and predominant nucleotide and amino acid sequences of the ISDR at initial and subsequent time points were compared for each patient. Three of 12 patients with the wild type ISDR (no amino acid mutation in the ISDR compared to the consensus sequence) changed to the intermediate type (1 to 3 mutations) at later time points, whereas the other 9 still had the wild type. Similarly, 2 of 18 patients with the intermediate type changed to the wild type, whereas the other 16 patients continued to have the intermediate type. One of 6 patients with the mutant type (4 or more mutations) changed to the intermediate type, and the other 5 continued to have the mutant type. Although ISDR nucleotide changes/site/year were not significantly different among the 3 groups of patients, percentages of non-synonymous nucleotide changes were greater in the mutant type (63%) than the wild (9%) or the intermediate type (20%) (P < 0.05). These results show that mutations in the ISDR do not occur frequently, suggesting that interferon sensitivity does not change greatly during the natural course of the disease in each patient.