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The "interferon sensitivity determining region" of hepatitis C virus is a stable sequence element.

Abstract：

BACKGROUND/AIMS:A sequence of 40 amino acids within the nonstructural protein 5A of hepatitis C virus (HCV) has been suggested to be an interferon sensitivity determining region (ISDR). The variations in the ISDR after 12-14 years of chronic infection and the correlation between ISDR and interferon response were studied in patients who were infected by the same HCV isolate. METHODS:We determined the HCV-ISDRs of 13 chronically infected patients by direct sequencing of polymerase chain reaction products. All patients were infected by isolate HCV-AD78, but differed with respect to their sensitivity to interferon. Four patients were complete responders, two patients were non-responders, and seven showed a partial response. RESULTS:The ISDR of HCV-AD78 differed from a prototypical HCV-1b sequence in one amino acid and was therefore classified as an intermediate type. Direct sequencing of the HCV-ISDRs of the patients 12-14 years after infection, but before interferon therapy, revealed a rate of 2.2x10(-3) nucleotide substitutions per site per year, resulting in only single intermediate type amino acid exchanges. All sequences ranked with the intermediate type. Moreover, during interferon treatment no selection to a wild type ISDR was observed in five partial responders. CONCLUSIONS:Within the homogeneous patient group examined here, no correlation was found between the ISDR and the interferon response. Recent studies found only a small number of mutant type ISDRs in Europe. Additionally, our results indicate that the ISDR is a stable sequence element. This provides an explanation for the divergent data relating to the importance of the ISDR in different geographical regions.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Rispeter K,Lu M,Zibert A,Wiese M,de Oliveira JM,Roggendorf M

doi

10.1016/s0168-8278(98)80051-2

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

352-61

issue

3

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(98)80051-2

journal_volume

29

pub_type

临床试验,杂志文章,随机对照试验

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