[Positive selection analysis of hepatitis C virus genotype 1b envelope 2 gene and its significance during natural chronic infection].
OBJECTIVE
To elucidate adaptive evolution patterns and perform a positive selection analysis of hepatitis C virus(HCV) genotype 1b envelope 2 gene(E2) during natural chronic infection by a longitudinal study.


METHODS
HCV E2 quasispecies profiles were derived from partially sequenced domains of 6 000 bp recombinant clones. Phylogenetic trees for HCV E2 gene were constructed by MEGA software and the specific codons undergoing diversifying positive selection were identified by FEL method.


RESULTS
HCV phylogenies, coupled with the number and distribution of selected sites were differed markedly between patients. HCV quasispecies complexity during chronic infection was not associated with the evolutionary time and the dominant viriant alternation of HCV quasispecies may occur after more than six months apart. Five sites under positive selection were identified within the ectodomain of the E2 protein.


CONCLUSIONS
A series of serum specimens for studies based on dominant viriant of HCV dynamic quasispecies is recommended to be collected at every six months. Several individual sites of HCV E2 gene are under a strong host immune pressure, position aa384, aa399 and aa410 may be involved in escape from neutralizing antibodies, while position aa475, aa522 may correlate to modulate the virus-receptor interaction which result in evading immunity.
Zhu
Yan
Y
Institute of Infectious Diseases of Chinese PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Mao
Qing
Q
Lan
Lin
L
Hu
Ya-jun
YJ
Tan
Zhao-xia
ZX
Zhang
Chang-jiang
CJ
Wang
Yu-ming
YM
Wang
Xiao-hong
XH
D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000145:classification* / Q000235:genetics / Q000378:metabolism*
D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus