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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{triangledown}

David J. Woollard,1,2* Gholamreza Haqshenas,1,3 Xuebin Dong,1,3 Bridget F. Pratt,4 Stephen J. Kent,4 and Eric J. Gowans1,3

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-{gamma}) 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-{gamma} 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.

* Corresponding author. Mailing address: The Burnet Institute, G.P.O. Box 2284, Melbourne, Victoria, Australia 3004. Phone: 61-3 9282-2205. Fax: 61-3 9282-2100. E-mail: woollard{at}burnet.edu.au

{triangledown} Published ahead of print on 19 December 2007.

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.





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