Virus-specific T-cell immunity correlates with control of GB virus B infection in marmosets.
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.
Woollard
David J
DJ
The Burnet Institute, G.P.O. Box 2284, Melbourne, Victoria, Australia. woollard@burnet.edu.au
Haqshenas
Gholamreza
G
Dong
Xuebin
X
Pratt
Bridget F
BF
Kent
Stephen J
SJ
Gowans
Eric J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D002144:Callithrix; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D029406:GB virus B / Q000276:immunology / Q000302:isolation & purification*; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D015395:Histocompatibility Antigens Class I