Nature Medicine：新方法可杀灭潜在艾滋病病毒-生物研究-生物谷

据参与研究工作的科学家介绍，这种新的治疗方法既可以杀灭在人体内四处游荡的病毒，还能够杀灭隐藏在免疫细胞内的病毒。该项研究成果的价值在于它为全世界研究艾滋病治疗的科学家指明了前进的方向，为找到一种全新的具有创新性的艾滋病治疗方法奠定了基础。相关文章6月21日在线发表于《自然—医学》。

迄今为止，抗艾滋病治疗的疗效一直不甚理想，原因是病毒隐藏在免疫系统细胞里，而目前使用的高效抗逆转录病毒疗法对躲藏在免疫细胞内的病毒无计可施。加拿大和美国的研究人员成功地识别出那些躲藏有病毒的细胞，找到了病毒可以逃避现有治疗的“隐身”机理。

参与研究工作的麦吉尔大学血液学家基恩·罗迪教授认为，该项研究成果首次证明所谓的艾滋病病毒潜伏池现象并不是因为抗逆转药物缺乏效力，而是由于病毒隐藏在两种不同类型的长寿命CD4记忆免疫细胞内。艾滋病病毒潜伏池有几种类型，每一种类型潜伏池都需要不同的治疗方法来消除它们。一旦病毒隐藏在这些潜伏池细胞里，它们就会对其产生依赖。如果细胞存活，病毒就可以存活，但如果细胞死亡，则病毒也无法存活。因此，消灭这些免疫细胞就能够杀灭这些隐藏其中的病毒。现存的高效抗逆转录病毒疗法可以杀灭在体内流传的病毒，但是无法对付隐藏在免疫系统细胞内的病毒。

主持研究工作的蒙特利尔大学塞卡里教授表示，该研究结果与用于治疗白血病采取的策略相似，即同样是定向化疗，并同时与定向免疫治疗相结合。这种方法既可以杀灭细胞中的病毒，同时也为免疫系统留出时间再生健康细胞。

研究人员认为，目前所得到的成果为开发出全新的抗艾滋病毒治疗方法提供了一个重要的选项，但要进入实际应用还需要若干年进一步的研究工作。（生物谷Bioon.com）

生物谷推荐原始出处：

Nature Medicine 21 June 2009 | doi:10.1038/nm.1972

HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation

Nicolas Chomont1,2,3, Mohamed El-Far1,2,3, Petronela Ancuta3, Lydie Trautmann1,2,3, Francesco A Procopio1,2,3, Bader Yassine-Diab1,2,3, Geneviève Boucher1, Mohamed-Rachid Boulassel4, Georges Ghattas5, Jason M Brenchley6, Timothy W Schacker7, Brenna J Hill8, Daniel C Douek8, Jean-Pierre Routy4,9, Elias K Haddad1,2,3,9 & Rafick-Pierre Sékaly1,2,3,9,10,11

Abstract

HIV persists in a reservoir of latently infected CD4+ T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (TCM) and transitional memory (TTM) CD4+ T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in TCM cells in subjects showing reconstitution of the CD4+ compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in TTM cells from aviremic individuals with low CD4+ counts and higher amounts of interleukin-7–mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.

1 Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) Saint-Luc, Montréal, Québec, Canada.
2 Laboratoire d'Immunologie, Département de Microbiologie et d'Immunologie, Université de Montréal, Québec, Canada.
3 Institute National de la Santé et de la Recherche Médicale U743, CR-CHUM, Université de Montréal, Montréal, Québec, Canada.
4 Immunodeficiency Service and Division of Hematology, Royal Victoria Hospital, McGill University Health Centre (MUHC), McGill University, Montréal, Québec, Canada.
5 Department of Gastroenterology, MUHC, Montréal, Québec, Canada.
6 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
7 Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
8 Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
9 Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
10 Department of Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA.
11 Vaccine and Gene Therapy Institute, Port-Ste Lucy, Florida, USA.