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Journal of Virology, March 2008, p. 3054-3060, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.01153-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Virus-Specific T-Cell Immunity Correlates with Control of GB Virus B Infection in Marmosets

The Burnet Institute, G.P.O. Box 2284, Melbourne, Victoria, Australia,¹ Department of Immunology, Monash University, Melbourne, Victoria, Australia,² Department of Microbiology, Monash University, Clayton, Victoria, Australia,³ Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia⁴

Received 28 May 2007/ Accepted 11 December 2007

GB virus B (GBV-B) is a hepatotropic virus that is closely related to hepatitis C virus (HCV). GBV-B causes acute hepatitis in infected marmosets and tamarins and is therefore a useful small-animal model for the study of HCV. We investigated virus-specific T-cell responses in marmosets infected with GBV-B. Gamma interferon (IFN-) enzyme-linked immunospot (ELISPOT) assay responses in the peripheral blood of two marmosets were assessed throughout the course of GBV-B infection. These T-cell responses were directed against the GBV-B nonstructural proteins 3 (NS3), 4A (NS4A), and 5B (NS5B), and their appearance was temporally associated with clearance of viremia. These marmosets were then rechallenged with GBV-B at least 3 months after clearance of the primary infection to determine if the animals were protected from reinfection. There was no detectable viremia following reinfection, although a sharp increase in T-cell responses against GBV-B proteins was observed. Epitope mapping of T-cell responses to GBV-B was performed with liver and blood samples from both marmosets after rechallenge with GBV-B. Three shared, immunodominant T-cell epitopes within NS3 were identified in animals with multiple common major histocompatibility complex class I alleles. IFN- ELISPOT responses were also detected in the livers of two marmosets that had resolved a primary GBV-B infection. These responses were high in frequency and were directed against epitopes within GBV-B NS3, NS4A, and NS5B proteins. These results indicate that virus-specific T-cell responses are detectable in the liver and blood of GBV-B-infected marmosets and that the clearance of GBV-B is associated with the appearance of these responses.

Published ahead of print on 19 December 2007.