生物谷报道:研究人员报告说,3个基因的DNA变异在不同个人对HIV感染早期响应上的极为不同起重要作用。人们一般认为,感染早期免疫系统抗击该病毒的能力与感染发展成艾滋病的快慢关联,了解个体对感染响应不同的基因基础对研究有效的治疗方法很重要。在HIV感染发展成艾滋病之前,病毒与免疫系统进入一个僵局,那时免疫系统调动其T细胞试图将快速增殖的病毒控制住。在这个阶段,人体中的病毒载量达到一个“稳定值”(set point),不同患者的稳定值有很大的不同。Jacques Fellay和同事搜寻了HIV感染者的基因组,发现3个基因的变异或多肽与稳定值的差别相关。发生在与免疫有关的基因上的两个多肽能解释不同患者病毒载量稳定值差别的15%。第三个多肽对疾病发展的贡献仍不清楚,该多肽发生在一个将其他基因打开或关闭的酶的一段编码上。文章作者提出,这种新的基因组范围的对HIV易感性的分析,对人类对付其他重要的病原体能力的不同应该能提供有用的信息。(科学时报)
原始出处:
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Published Online July 19, 2007
Science DOI: 10.1126/science.1143767
Submitted on April 13, 2007
Accepted on July 3, 2007
A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1
Jacques Fellay 1, Kevin V. Shianna 2, Dongliang Ge 1, Sara Colombo 3, Bruno Ledergerber 4, Mike Weale 1, Kunlin Zhang 3, Curtis Gumbs 1, Antonella Castagna 5, Andrea Cossarizza 6, Alessandro Cozzi-Lepri 7, Andrea De Luca 8, Philippa Easterbrook 9, Patrick Francioli 10, Simon Mallal 11, Javier Martinez-Picado 12, José M. Miro 13, Niels Obel 14, Jason P. Smith 2, Josiane Wyniger 3, Patrick Descombes 15, Stylianos E. Antonarakis 16, Norman L. Letvin 17, Andrew J. McMichael 18, Barton F. Haynes 19, Amalio Telenti 3*, David B. Goldstein 1*
1 Center for Population Genomics and Pharmacogenetics, Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.
2 Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.
3 Institute of Microbiology, University Hospital Center and University of Lausanne, 1011 Lausanne, Switzerland.
4 Division of Infectious Diseases, University Hospital, 8091 Zürich, Switzerland.
5 Clinic of Infectious Diseases, IRCCS San Raffaele Hospital, 20127 Milan, Italy.
6 Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia, School of Medicine, 41100 Modena, Italy.
7 Department of Primary Care and Population Sciences, Royal Free and University College Medical School, UCL London NW3 2PF, UK.
8 Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, 00168 Rome, Italy.
9 Academic Department of HIV/GUM, Kings College London, at Guy's, King's, and St Thomas' Hospitals, London SE5 9RJ, UK.
10 Service of Infectious Diseases, Department of Medicine and Service of Hospital Preventive Medicine, University Hospital Center, 1011 Lausanne, Switzerland.
11 Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, WA 6000, Australia.
12 irsiCaixa Foundation and Hospital Germans Trias i Pujol, 08916 Badalona, Spain, and Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
13 Hospital Clinic - IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
14 Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark.
15 Genomics Platform, NCCR "Frontiers in Genetics," University of Geneva, 1211 Geneva, Switzerland.
16 Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
17 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
18 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
19 Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.
* To whom correspondence should be addressed.
Amalio Telenti , E-mail: amalio.telenti@chuv.ch
David B. Goldstein , E-mail: d.goldstein@duke.edu
Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele HLA-B*5701, while a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated a third locus encoding a RNA polymerase subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.