title: Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells.
abstract: The progressive depletion of CD4 T cells underlies clinical progression to AIDS in untreated HIV-infected subjects. Most dying CD4 T cells correspond to resting nonpermissive cells residing in lymphoid tissues. Death is due to an innate immune response against the incomplete cytosolic viral DNA intermediates accumulating in these cells. The viral DNA is detected by the IFI16 sensor, leading to inflammasome assembly, caspase-1 activation, and the induction of pyroptosis, a highly inflammatory form of programmed cell death. We now show that cell-to-cell transmission of HIV is obligatorily required for activation of this death pathway. Cell-free HIV-1 virions, even when added in large quantities, fail to activate pyroptosis. These findings underscore the infected CD4 T cells as the major killing units promoting progression to AIDS and highlight a previously unappreciated role for the virological synapse in HIV pathogenesis.
authors: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158.
authors: Nicole Lk
authors: NL
authors: Galloway
authors: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158.
authors: Gilad
authors: G
authors: Doitsh
authors: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158.
authors: Kathryn M
authors: KM
authors: Monroe
authors: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158.
authors: Zhiyuan
authors: Z
authors: Yang
authors: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158.
authors: Isa
authors: I
authors: Muñoz-Arias
authors: Department of Basic Sciences and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA.
authors: David N
authors: DN
authors: Levy
authors: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158.|Department of Medicine, University of California, San Francisco, San Francisco, CA 94143.|Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.
authors: Warner C
authors: WC
authors: Greene
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D020170:Caspase 1 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008221:Lymphoid Tissue / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D020170:Caspase 1