Sequence variations of the hypervariable region of hepatitis C virus and their clinical significance.
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-polymerase chain reaction (RT-PCR) and direct sequencing methods.


RESULTS
HCV-HVR sequences of the 28 patients changed in various degrees. 92% of these nucleotide substitutions led to changes of corresponding aminoacid sequences. 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 was 0.89 x 10(-1) per genome site per year in acute hepatitis C, compared with 2.31 x 10(-1) per genome site per year in chronic hepatitis C (P < 0.05), but had no relation to HCV subtype. Variation of HVR in the flare up type (ALT > 150 mu/L) was much more than that in the quiescent type (ALT < 100 mu/L).


CONCLUSIONS
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.
Zhang
S
S
Department of Gastroenterology, Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China.
Wang
W
W
Zhou
K
K
Liu
H
H
D000208:Acute Disease; D000328:Adult; D019943:Amino Acid Substitution; D024141:Collagen Type IV / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000378:metabolism / Q000473:pathology / Q000821:virology; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D013997:Time Factors
D024141:Collagen Type IV; D018076:DNA, Complementary; D012367:RNA, Viral