生物谷報道：研究人員報告說,，3個基因的DNA變異在不同個人對HIV感染早期響應上的極為不同起重要作用。人們一般認為,，感染早期免疫系統(tǒng)抗擊該病毒的能力與感染發(fā)展成艾滋病的快慢關(guān)聯(lián),，了解個體對感染響應不同的基因基礎(chǔ)對研究有效的治療方法很重要。在HIV感染發(fā)展成艾滋病之前,，病毒與免疫系統(tǒng)進入一個僵局,，那時免疫系統(tǒng)調(diào)動其T細胞試圖將快速增殖的病毒控制住。在這個階段,，人體中的病毒載量達到一個“穩(wěn)定值”(set point),，不同患者的穩(wěn)定值有很大的不同。Jacques Fellay和同事搜尋了HIV感染者的基因組,，發(fā)現(xiàn)3個基因的變異或多肽與穩(wěn)定值的差別相關(guān),。發(fā)生在與免疫有關(guān)的基因上的兩個多肽能解釋不同患者病毒載量穩(wěn)定值差別的15%。第三個多肽對疾病發(fā)展的貢獻仍不清楚,，該多肽發(fā)生在一個將其他基因打開或關(guān)閉的酶的一段編碼上,。文章作者提出，這種新的基因組范圍的對HIV易感性的分析,，對人類對付其他重要的病原體能力的不同應該能提供有用的信息,。（科學時報）
原始出處:
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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: [email protected]
David B. Goldstein , E-mail: [email protected]
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.
