Article abstract
Nature Medicine 15, 893 - 900 (2009)
Published online: 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.
- Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) Saint-Luc, Montréal, Québec, Canada.
- Laboratoire d'Immunologie, Département de Microbiologie et d'Immunologie, Université de Montréal, Québec, Canada.
- Institute National de la Santé et de la Recherche Médicale U743, CR-CHUM, Université de Montréal, Montréal, Québec, Canada.
- Immunodeficiency Service and Division of Hematology, Royal Victoria Hospital, McGill University Health Centre (MUHC), McGill University, Montréal, Québec, Canada.
- Department of Gastroenterology, MUHC, Montréal, Québec, Canada.
- Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
- Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
- Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
- Department of Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA.
- Vaccine and Gene Therapy Institute, Port-Ste Lucy, Florida, USA.
Correspondence to: Rafick-Pierre Sékaly1,2,3,9,10,11 e-mail: rafick-pierre.sekaly@umontreal.ca
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