[Genetic variation characteristics of the envelope region of hepatitis C virus in the patients with chronic hepatitis].
OBJECTIVE
To study the association of the envelope region variation of hepatitis C virus (HCV) with the chronicity of HCV infection.


METHODS
Acute phase plasma samples from three injection drug users who acquired HCV infection during six month follow-up and three patients with chronic hepatitis C were obtained. A 573 bp fragment containing the 5' half of E1 and 3' half of E2 were amplified by nested reverse transcription polymerase chain reaction (RT-PCR). For each cloned cDNAs were examined by a method that combined heteroduplex (HD) analysis and a single-stranded conformational polymorphism (SSCP) assay to assess quasispecies complexity and optimize selection of clones with unique gel shift patterns for sequencing. The ratio of nonsynonymous to synonymous substitution (dN/dS) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns and glycosylation signals.


RESULTS
Quasispecies complexity and E2 dN/dS ratio were higher in those with chronic hepatitis, in whom a trend toward more numbers of nonsynonymous mutations was detected at the E2. 1.02% (1.33/130) and 8.46% (11/130) amino acids within the E2 region mutated in chronic hepatitis and acute hepatitis, whereas within the E1 region 2.74% and 1.09% amino acids replaced among chronic and acute hepatitis respectively. Some consistent amino acids were detected, although the hypervariable region 1 (HVR1) had a higher variability in subjects with chronic infection.


CONCLUSIONS
HCV persistence is associated with a complex quasispecies and host immune selection to HVR1.
Chen
Song
S
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Wang
Yuming
Y
D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics*
D014759:Viral Envelope Proteins