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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
- 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.
- Subjects :
- Male
China
Hepatitis B virus
Molecular Sequence Data
Immunology
Adaptation, Biological
Epitopes, T-Lymphocyte
Human leukocyte antigen
Biology
medicine.disease_cause
Microbiology
Virus
Epitope
Hepatitis B, Chronic
Antigen
HLA Antigens
Virology
Genotype
medicine
Humans
Amino Acid Sequence
Hepatitis B e Antigens
Prospective Studies
Phylogeny
Polymorphism, Genetic
Australia
virus diseases
Hepatitis B
medicine.disease
digestive system diseases
HBeAg
Insect Science
Host-Pathogen Interactions
Pathogenesis and Immunity
Female
Subjects
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