在携带特别遗传风险因子的个体身上，艾滋病病毒（HIV）导致的疾病会以更快的速度发展，这一最新的研究成果发表在10月在线出版的《自然—免疫学》期刊上。
由Sunil Ahuja领导的一个HIV研究小组研究了一种特别的风险因子，它能显著预报HIV疾病的发展结果。综合携带CCR5和CCL3L1两种基因的个体更容易降低免疫反应，导致CD4+ T免疫细胞的大量减少，这两种现象均是进展性HIV疾病的特点。
新发现具有两方面的重要性。以前的研究表明，这两种基因的影响非常有限，而新发现则指出了它们显著的影响力，新发现还意味着能够用更有效的方法来预测HIV疾病的发展进程。（科学时报）
原始出处:
Nature Immunology
Published online: 21 October 2007 | doi:10.1038/ni1521
CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms
Matthew J Dolan1,2,3,16, Hemant Kulkarni4,16, Jose F Camargo4, Weijing He4, Alison Smith5, Juan-Manuel Anaya6, Toshiyuki Miura7,8,9, Frederick M Hecht10, Manju Mamtani4, Florencia Pereyra7,8,9, Vincent Marconi1,2, Andrea Mangano11, Luisa Sen11, Rosa Bologna12, Robert A Clark4, Stephanie A Anderson1,2,3, Judith Delmar1,2, Robert J O'Connell1,2, Andrew Lloyd13, Jeffrey Martin14, Seema S Ahuja4, Brian K Agan1,2,3, Bruce D Walker7,8,9, Steven G Deeks10 & Sunil K Ahuja4,15
Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry–independent mechanisms.
Infectious Disease Clinical Research Program, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA.
Infectious Diseases Service, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA.
Henry M. Jackson Foundation, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA.
Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, and Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
School of Psychology, University of Western Sydney, Penrith Sth, New South Wales 1797, Australia.
Cellular Biology and Immunogenetics Unit, Corporación para Investigaciones Biologicas–University of Rosario, Cra 72 78-B-141, Medellin, Colombia.
Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Division of AIDS, Harvard Medical School, Boston, Massachusetts 02114, USA.
Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.
Department of Medicine, University of California, and San Francisco General Hospital, San Francisco, California 94110, USA.
Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría "J.P. Garrahan", Buenos Aires 1245, Argentina.
Servicio de Infectología, Hospital de Pediatría "J.P. Garrahan", Buenos Aires 1245, Argentina.
School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94107, USA.
Department of Microbiology & Immunology and Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
These authors contributed equally to this work.
Correspondence to: Sunil K Ahuja4,15 e-mail: ahujas@uthscsa.edu
Correspondence to: Matthew J Dolan1,2,3,16 e-mail: mdolan@hjf.org
