生物谷：美國科學家在7月19日的《科學》在線版上發(fā)表論文稱,，他們初步揭示了為什么有些人能更好地抵抗艾滋病毒（HIV）。這將有助于開發(fā)出抗艾藥新的藥靶,。
HIV感染人體后,，其破壞人體免疫系統(tǒng)的速度決定于人體的最初反應(yīng)。乍一感染,，HIV水平會急速上升,，但是很快人體免疫系統(tǒng)和細胞產(chǎn)生的其它抗病毒因子就會使血液中的HIV水平下降，并建立一個“臨界點”（set point）,。臨界點越低,，免疫系統(tǒng)有效抵御病毒的時間就會越長。
為了弄清其中的機制,，由美國杜克大學遺傳學家David Goldstein領(lǐng)導的小組對此進行了研究,。他們研究了486位感染HIV的患者，這些患者的感染時間和臨界點均很清楚，并且尚未接受任何治療,。研究人員核對了來自DNA序列或單核苷酸多態(tài)性（single-nucleotide polymorphisms,，簡稱SNP）的已知50萬種變化。他們發(fā)現(xiàn)有兩種多態(tài)性能說明病毒臨界點中15%的變化,。這兩種多態(tài)性的作用彼此互不相干,，但是均與臨界點的降低有關(guān)。
其中一種多態(tài)性作用較強,，發(fā)生在含有HCP5基因（該基因編碼一種人體內(nèi)生型逆轉(zhuǎn)錄酶病毒）的DNA片斷或多態(tài)性中,。研究人員發(fā)現(xiàn)體內(nèi)含有該種多態(tài)性的患者往往還具有一種稀有基因，該基因名為HLA-B*5701,，能夠通過清除體內(nèi)感染HIV細胞強力抵抗HIV,。另外一種多態(tài)性存在于HLA-C基因中，該基因在促進免疫系統(tǒng)有效運作方面與HLA-B作用類似,。研究人員表示,，關(guān)于這兩種多態(tài)性降低病毒臨界點的機制，目前尚不清楚,。一旦弄清,，將會有助于開發(fā)出抗艾藥新的藥靶及新疫苗。
美國西北大學艾滋病研究人員Steven Wolinsky認為,，該項研究很令人激動,，但是主要關(guān)注的是白種人。如果研究對象的遺傳背景能夠更廣闊一些,，那么將會更加令人信服。（科學網(wǎng) 梅進/編譯）
原始出處:
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Published Online July 19, 2007
Science DOI: 10.1126/science.1143767
Reports
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.
