Development of a primary tamarin hepatocyte culture system for GB virus-B: A surrogate model for hepatitis C virus

B. Beames, D. Chavez, B. Guerra, L. Notvall, K. M. Brasky, R. E. Lanford

    Research output: Contribution to journalArticlepeer-review

    65 Scopus citations

    Abstract

    GB virus-B (GBV-B) causes an acute hepatitis in tamarins characterized by increased alanine transaminase levels that quickly return to normal as the virus is cleared. Phylogenetically, GBV-B is the closest relative to hepatitis C virus (HCV), and thus GBV-B infection of tamarins represents a powerful surrogate model system for the study of HCV. In this study, the course of infection of GBV-B in tamarins was followed using a real-time 5′ exonuclease (TaqMan) reverse transcription-PCR assay to determine the level of GBV-B in the serum. Peak viremia levels exceeded 109 genome equivalents/ml, followed by viral clearance within 14 to 16 weeks. Rechallenge of animals that had cleared infection resulted in viremia that was limited to 1 week, suggestive of a strong protective immune response. A robust tissue culture system for GBV-B was developed using primary cultures of tamarin hepatocytes. Hepatocytes obtained from a GBV-B-infected animal maintained high levels of cell-associated viral RNA and virion secretion for 42 days of culture. In vitro infection of normal hepatocytes resulted in rapid amplification of cell-associated viral RNA and secretion of up to 107 genome equivalents/ml of culture supernatant. In addition, infection could be monitored by immunofluorescence staining for GBV-B nonstructural NS3 protein. This model system overcomes many of the current obstacles to HCV research, including low levels of viral replication, lack of a small primate animal model, and lack of a reproducible tissue culture system.

    Original languageEnglish (US)
    Pages (from-to)11764-11772
    Number of pages9
    JournalJournal of virology
    Volume74
    Issue number24
    DOIs
    StatePublished - 2000

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

    Fingerprint

    Dive into the research topics of 'Development of a primary tamarin hepatocyte culture system for GB virus-B: A surrogate model for hepatitis C virus'. Together they form a unique fingerprint.

    Cite this