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Viral Adaptation to Host Immune Responses Occurs in Chronic Hepatitis B Virus (HBV) Infection, and Adaptation Is Greatest in HBV e Antigen-Negative Disease

Authors :
Anna Ayres
Abha Chopra
Simon Mallal
Jennifer Audsley
Katja Pfafferott
Stuart K. Roberts
Sharon R Lewin
Stephen Locarnini
Paul V. Desmond
Christopher P Desmond
Peter Revill
Silvana Gaudieri
Adam Gordon
Ian James
George K. K. Lau
Sarah Chivers
Scott Bowden
Caroline F Day
Alexander J. Thompson
Source :
Journal of Virology. 86:1181-1192
Publication Year :
2012
Publisher :
American Society for Microbiology, 2012.

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 not clear whether 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 the 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 were undertaken for treatment-naïve individuals (52% with genotype B, 48% with genotype C, 63% HBV e antigen [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 scores for binding between peptides containing these polymorphisms and associated HLA types. Among the regions that could be tested, HLA binding was predicted for 14/18 (78%). We identified several HLA-associated polymorphisms involving likely known anchor residues that 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 = 0.003). Thus, HBV appears to be under immune pressure in chronic HBV infection, particularly in HBeAg-negative disease.

Details

ISSN :
10985514 and 0022538X
Volume :
86
Database :
OpenAIRE
Journal :
Journal of Virology
Accession number :
edsair.doi.dedup.....e1c90c8158ef1db6bf90c7cecc52dcdd
Full Text :
https://doi.org/10.1128/jvi.05308-11