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标题: Viral adaptation to host immune responses occurs in chronic hepatitis B virus in [打印本页]
作者: StephenW 时间: 2011-11-14 14:46 标题: Viral adaptation to host immune responses occurs in chronic hepatitis B virus in
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]
作者: StephenW 时间: 2011-11-14 14:47
摘要
乙型肝炎病毒(HBV)特异性T细胞反应是重要的HBV感染的自然史。已知的HBV特异性T细胞表位的数量是有限的,如果病毒进化发生在慢性乙肝病毒感染,目前还不清楚。我们的目的是确定在一个大型的前瞻性诊所基于在澳大利亚和中国的亚洲慢性乙肝病毒感染患者的队列研究HBV序列变异和人类白细胞抗原(HLA)类型之间的关系(N= 119)小说乙肝病毒T细胞表位。在治疗过的人(52%48%,C基因型,B基因型,63%HBeAg阳性)进行了高分辨率的4位类HLA- I和II打字和全长的HBV测序。 HLA类型和HBV序列变异之间的统计学显著协会(N= 49),在HBV基因组在41个地点。使用预测方案,我们确定了肽之间含有这些基因多态性及相关的HLA类型的具有约束力的分数。 HLA的具有约束力的地区可以进行测试,被预测为14/18(78%)。我们确定了几个相关的HLA基因多态性,涉及可能已知的锚定残基,导致在改变预测约束力的分数。一些相关HLA多态性与匹配的HLA -限制范围内已知的T细胞表位。增强病毒适应化修改(定义为有关HLA和逃脱的氨基酸存在)HBeAg阴性患者(P = 0.003)独立相关。因此,HBV似乎是慢性乙肝病毒感染的免疫压力下,特别是在HBeAg阴性的疾病。
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