Chronic infection with human hepatitis B virus (HBV) leads to liver damage, cirrhosis and liver cancer. The applicant's goal is to elucidate the molecular basis of pathogenicity, chronicity, and clearance of HBV infection. Although chronicity has been attributed to host factors, such as the immune response, viral factors per se have remained largely uninvestigated. The applicant's preliminary results suggest that in chronic carriers and hepatoma patients HBV-acquired mutations may cause antigenic changes that lead to escape from the immune system. They propose to test more directly and definitively the hypothesis that accumulation of certain viral mutations is crucial for the persistence of pathogenic HBV during its long term interaction with the host. The immunopathological interactions between certain HBV core antigen mutants and the host will be studied via assays for peptide-major histocompatibility complex (peptide-MHC) binding, antigen processing and T cell receptor recognition. Specifically, three aims are proposed:
Aim 1) to test the hypothesis that certain core antigen mutations affect MHC-peptide binding;
Aim 2) to test the hypothesis that aberrant HBV core antigen processing could result from immune escape mutants;
Aim 3) to test the hypothesis that certain core antigen mutations affect TCR peptide-MHC recognition. This last aim may be expanded to include the examination of TCR-antagonistic or agonistic mutant core antigens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070336-02
Application #
2608145
Study Section
Special Emphasis Panel (ZRG2-MEP (02))
Program Officer
Cole, John S
Project Start
1996-12-23
Project End
1999-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Pathology
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
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Tai, Pei-Ching; Suk, Fat-Moon; Gerlich, Wolfram H et al. (2002) Hypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants. Virology 292:44-58
Sahu, Gautam Kumar; Tai, Pei-Ching; Chatterjee, Soma Banerjee et al. (2002) Out-of-frame versus in-frame core internal deletion variants of human and woodchuck hepatitis B viruses. Virology 292:35-43

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