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 journalArticle

63 Citations (Scopus)

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
Externally publishedYes

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Hepatitis GB virus B
GB virus B
Hepatitis C virus
Callitrichidae
Hepacivirus
hepatocytes
Hepatocytes
infection
Viremia
viremia
Viral RNA
Infection
tissue culture
animal models
Phosphodiesterase I
secretion
Genome
RNA
genome
hepatitis

ASJC Scopus subject areas

  • Immunology

Cite this

Development of a primary tamarin hepatocyte culture system for GB virus-B : A surrogate model for hepatitis C virus. / Beames, B.; Chavez, D.; Guerra, B.; Notvall, L.; Brasky, K. M.; Lanford, R. E.

In: Journal of Virology, Vol. 74, No. 24, 2000, p. 11764-11772.

Research output: Contribution to journalArticle

Beames, B. ; Chavez, D. ; Guerra, B. ; Notvall, L. ; Brasky, K. M. ; Lanford, R. E. / Development of a primary tamarin hepatocyte culture system for GB virus-B : A surrogate model for hepatitis C virus. In: Journal of Virology. 2000 ; Vol. 74, No. 24. pp. 11764-11772.
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