http://jvi.asm.org/content/early/2011/11/04/JVI.05308-11.abstract?cited-by=yes&legid=jvi;JVI.05308-11v1
Viral adaptation to host immune responses occurs in chronic hepatitis B virus infection and adaptation is greatest in HBeAg negative disease - Christopher P. Desmond1,2,
- Silvana Gaudieri3,4,
- Ian R. James3,
- Katja Pfafferott3,
- Abha Chopra3,
- George K. Lau5,6,
- Jennifer Audsley2,
- Caroline Day7,
- Sarah Chivers7,
- Adam Gordon1,7,
- Peter A. Revill8,
- Scott Bowden8,
- Anna Ayres8,
- Paul V. Desmond9,10,
- Alexander J. Thompson8,9,
- Stuart K. Roberts1,
- Stephen A. Locarnini8,
- Simon A. Mallal3,11 and
- Sharon R. Lewin2,12,13↴
- Author Affiliations - 1Department of Gastroenterology, The Alfred, Melbourne, Australia
- 2Department of Medicine, Monash University, Melbourne, Australia
- 3Institute of Immunology and Infectious Diseases, Murdoch University, Western Australia, Australia
- 4Centre for Forensic Science and School of Anatomy and Human Biology, University of Western Australia, Western Australia, Australia
- 5Research Centre of Infection and Immunology, The University of Hong Kong
- 6Department of Medicine, Queen Mary Hospital, The University of Hong Kong
- 7Department of Gastroenterology, Box Hill Hospital, Melbourne, Australia
- 8Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
- 9Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
- 10Department of Medicine, University of Melbourne
- 11Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Western Australia, Australia
- 12Infectious Diseases Unit, The Alfred, Melbourne, Australia
- 13Centre for Virology, Burnet Institute, Melbourne, Australia
ABSTRACT Hepatitis B virus (HBV)-specific T-cell responses are important in the natural history of HBV infection. The number of known HBV-specific T-cell epitopes is limited and it is unclear if viral evolution occurs in chronic HBV infection. We aimed to identify novel HBV T-cell epitopes by examining the relationship between HBV sequence variation and Human leukocyte antigen (HLA) type in a large prospective clinic based cohort of Asian patients with chronic HBV infection recruited in Australia and China (n=119). High-resolution 4-digit HLA class-I and II typing and full-length HBV sequencing was undertaken in treatment-naïve individuals (52% genotype B, 48% genotype C, 63% HBeAg-positive). Statistically significant associations between HLA types and HBV sequence variation were identified (n=49) at 41 sites in the HBV genome. Using prediction programs we determined binding scores between peptides containing these polymorphisms and associated HLA types. Of the regions able to be tested, HLA binding was predicted for 14/18 (78%). We identified several HLA-associated polymorphisms that involved likely known anchor residues which resulted in altered predicted binding scores. Some HLA-associated polymorphisms fell within known T-cell epitopes with matching HLA-restriction. Enhanced viral adaptation (defined as the presence of the relevant HLA and the escaped amino acid) was independently associated with HBeAg-negative disease (P=.003). Thus, HBV appears to be under immune pressure in chronic HBV infection, particularly in HBeAg-negative disease.
FOOTNOTES - Correspondence address: Professor Sharon R Lewin, Infectious Diseases Unit, The Alfred, Level 2, Burnet Building, 85 Commercial Road, Melbourne, Victoria 3004, Australia, Telephone: (613) 9076 8491, Fax: (613) 9076 2431, [email protected]
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