PMID- 22072755 OWN - NLM STAT- MEDLINE DCOM- 20120222 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 86 IP - 2 DP - 2012 Jan TI - Viral adaptation to host immune responses occurs in chronic hepatitis B virus (HBV) infection, and adaptation is greatest in HBV e antigen-negative disease. PG - 1181-92 LID - 10.1128/JVI.05308-11 [doi] AB - 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-naive 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. FAU - Desmond, Christopher P AU - Desmond CP AD - Department of Gastroenterology, The Alfred, Melbourne, Australia. FAU - Gaudieri, Silvana AU - Gaudieri S FAU - James, Ian R AU - James IR FAU - Pfafferott, Katja AU - Pfafferott K FAU - Chopra, Abha AU - Chopra A FAU - Lau, George K AU - Lau GK FAU - Audsley, Jennifer AU - Audsley J FAU - Day, Caroline AU - Day C FAU - Chivers, Sarah AU - Chivers S FAU - Gordon, Adam AU - Gordon A FAU - Revill, Peter A AU - Revill PA FAU - Bowden, Scott AU - Bowden S FAU - Ayres, Anna AU - Ayres A FAU - Desmond, Paul V AU - Desmond PV FAU - Thompson, Alexander J AU - Thompson AJ FAU - Roberts, Stuart K AU - Roberts SK FAU - Locarnini, Stephen A AU - Locarnini SA FAU - Mallal, Simon A AU - Mallal SA FAU - Lewin, Sharon R AU - Lewin SR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111109 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (Hepatitis B e Antigens) SB - IM MH - Adaptation, Biological MH - Amino Acid Sequence MH - Australia MH - China MH - Epitopes, T-Lymphocyte/genetics/immunology MH - Female MH - HLA Antigens/*genetics/*immunology MH - Hepatitis B e Antigens/*blood/genetics/immunology MH - Hepatitis B virus/classification/genetics/immunology/*physiology MH - Hepatitis B, Chronic/genetics/*immunology/*virology MH - Host-Pathogen Interactions MH - Humans MH - Male MH - Molecular Sequence Data MH - Phylogeny MH - Polymorphism, Genetic MH - Prospective Studies PMC - PMC3255822 EDAT- 2011/11/11 06:00 MHDA- 2012/02/23 06:00 PMCR- 2012/07/01 CRDT- 2011/11/11 06:00 PHST- 2011/11/11 06:00 [entrez] PHST- 2011/11/11 06:00 [pubmed] PHST- 2012/02/23 06:00 [medline] PHST- 2012/07/01 00:00 [pmc-release] AID - JVI.05308-11 [pii] AID - 5308-11 [pii] AID - 10.1128/JVI.05308-11 [doi] PST - ppublish SO - J Virol. 2012 Jan;86(2):1181-92. doi: 10.1128/JVI.05308-11. Epub 2011 Nov 9.