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

Stuart C. Ray, Qing Mao, Robert E. Lanford, Suzanne Bassett, Oliver Laeyendecker, Yu Ming Wang, David L. Thomas

    Research output: Contribution to journalArticlepeer-review

    62 Scopus citations


    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 hetero-duplex- 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.

    Original languageEnglish (US)
    Pages (from-to)3058-3066
    Number of pages9
    JournalJournal of virology
    Issue number7
    StatePublished - 2000

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology


    Dive into the research topics of 'Hypervariable region 1 sequence stability during hepatitis C virus replication in chimpanzees'. Together they form a unique fingerprint.

    Cite this