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J. Virol. doi:10.1128/JVI.02711-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Acute resolving Woodchuck Hepatitis Virus infection is associated with a strong CTL response to a single WHV core peptide

Institute of Virology, University Hospital Essen, University Duisburg-Essen, Germany

^* To whom correspondence should be addressed. Email: michael.roggendorf{at}uni-due.de.

	Abstract

Woodchucks infected with Woodchuck Hepatitis Virus (WHV) are an excellent model for studying acute self-limited and chronic hepadnaviral infection. Defects in the immunological response leading to chronicity are still unknown. Specific T helper cell responses to WHV core and surface antigens (WHcAg, WHsAg) are associated with acute resolving infection, however they are undetectable in chronic infection. Up to now, cytotoxic T lymphocyte (CTL) responses could not be determined in the woodchuck. In the present study, we detected virus-specific CTL responses by a CD107a degranulation assay. Splenocytes of post-acutely WHV-infected woodchucks (18 months post infection) were isolated and stimulated with overlapping peptides covering the whole WHcAg. After six days, cells were restimulated and stained for CD3 and CD107a. One peptide (c96-110) turned out to be accountable for T cell expansion and CD107a-staining. Further on, we applied the optimized degranulation assay to study the kinetics of T cell response in acute WHV-infection. We found a vigorous T cell response against peptide c96-110 using peripheral blood cells (PBMC) beginning at the peak of viral load (week 5) and lasting up to 15 weeks post infection. In contrast, there was no T cell response against peptide c96-110 detectable in chronically WHV-infected animals. Thus, with this newly established flow cytometric degranulation assay we detected for the first time virus-specific CTL and determined one immunodominant epitope of WHcAg in the woodchuck.