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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 amino acid 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 89×10 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 relation 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
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 amino acid sequences Only 8% of changed nucleotide was 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 × 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 relation 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 μL) 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