title: HIV-1 integration landscape during latent and active infection.
abstract: The barrier to curing HIV-1 is thought to reside primarily in CD4(+) T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4(+) T cells that remain relatively quiescent.
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Lillian B
authors: LB
authors: Cohn
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; National Institute of Science and Technology in Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Catão Roxo, 2501, Ribeirão Preto CEP 14051-140, Brazil.
authors: Israel T
authors: IT
authors: Silva
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Thiago Y
authors: TY
authors: Oliveira
authors: Departamento de Computação e Matemática, Universidade de São Paulo. Av. Bandeirantes, 3900, Ribeirão Preto CEP 14049-901, Brazil.
authors: Rafael A
authors: RA
authors: Rosales
authors: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Erica H
authors: EH
authors: Parrish
authors: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Gerald H
authors: GH
authors: Learn
authors: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Beatrice H
authors: BH
authors: Hahn
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: Julie L
authors: JL
authors: Czartoski
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors: M Juliana
authors: MJ
authors: McElrath
authors: Department I of Internal Medicine, University Hospital of Cologne, 50924 Cologne, Germany; German Centre for Infection Research, partner site Bonn-Cologne, 50924 Cologne, Germany.
authors: Clara
authors: C
authors: Lehmann
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Florian
authors: F
authors: Klein
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Marina
authors: M
authors: Caskey
authors: Ragon Institute of MGH, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors: Bruce D
authors: BD
authors: Walker
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Janet D
authors: JD
authors: Siliciano
authors: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Robert F
authors: RF
authors: Siliciano
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Mila
authors: M
authors: Jankovic
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: nussen@rockefeller.edu.
authors: Michel C
authors: MC
authors: Nussenzweig
mesh_terms: D020087:Alu Elements; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002999:Clone Cells; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D011533:Proviruses / Q000502:physiology; D059010:Single-Cell Analysis; D016662:Virus Integration; D017735:Virus Latency
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