Hypervariable region 1 sequence stability during hepatitis C virus replication in chimpanzees.

Abstract:

:The putative envelope 2 (E2) gene of hepatitis C virus (HCV) contains a highly variable region referred to as hypervariable region 1 (HVR1). We hypothesized that this genetic variability is driven by immune selection pressure, rather than representing the accumulation of random mutations in a region with relatively little functional constraint. To test this hypothesis, we examined the E2 sequence of a human inoculum that was passaged through eight chimpanzees, which appear to have a replicative rate (opportunity for chance mutation) similar to that of humans. Acute-phase plasma samples from a human (the inoculum) and six of eight serially infected chimpanzees were studied. For each, 33 cloned cDNAs were examined by a combined heteroduplex-single-stranded conformational polymorphism assay to assess quasispecies complexity and optimize selection of clones with unique gel shift patterns (clonotypes) for sequencing. The sequence diversity of HCV was significantly lower in the chimpanzees than in the humans, and during eight serial passages there was no change in the sequence of the majority clonotype from each animal examined. Similarly, the rates of protein sequence altering (nonsynonymous) substitution were lower in the chimpanzees than in the humans. These findings demonstrate that nonsynonymous mutations indicate selection pressure rather than being an incidental result of HCV replication.

journal_name

J Virol

journal_title

Journal of virology

authors

Ray SC,Mao Q,Lanford RE,Bassett S,Laeyendecker O,Wang YM,Thomas DL

doi

10.1128/jvi.74.7.3058-3066.2000

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

3058-66

issue

7

eissn

0022-538X

issn

1098-5514

journal_volume

74

pub_type

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