Sequence variations of the hypervariable region of hepatitis C virus and their clinical significance

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Author:
ZHANG Shunca()
WANG Wei()
ZHOU Kang()
LIU Houyu()
Journal Title:
CHINESE MEDICAL JOURNAL
Issue:
Volume 113, Issue 12, 2000
DOI:
Key Word:
hepatitis C;hepatitis C virus hypervariable region;sequence analysis;reverse transcription polymemse chain reaction;Type Ⅳ collaqen

Abstract: Objective To understand the clinical significance of sequence variations in the hypervariable region (HVR) of hepatitis C virus during infection. Methods Eight patients with acute hepatitis C and 20 patients with chronic hepatitis C were followed up for two years. Blood samples were taken at intervals of six months for analysis of HCV-HVR sequences by reverse transcription-pelymerase chain reaction (RT-PCR) and direct sequencing methods. Results HCV-HVR sequences of the 28 patients changed in various degrees. 92% of these nuclentide substitutions led to changes of corresponding amino acid sequence. Only 8% of changed nucleotide were synonymous substitutions. Of 27 amino acids variation of amino acid ranged from 1 to 20 (mean 8, 30%). The most common nucleotide substitution (62%) occurred in the first position of codon, 31% in the second and the rest in the third. HVR variation rate wes 0.89×10-1 per genome site per year in acute hepatitis C, compared with 2.31×10-1 per genome site per year in chronic hepatitis C (P<0.05), but had no relafian to HCV subtype. Variation of HVR in the flare up type (ALT>150 μ/L) was much more than that in the quiescent type (ALT<100 μ/L). Conclusion Our results suggested that sequence variation of HVR during HCV chronic infection seems to be an adaptive response to HCV to evade the host immune pressure and might play a major role in the establishment of persistent infection as well as in the flare-up of hepatitis.

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