title: Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting cells to CD4(+) target cells.
abstract: Antigen-presenting cells (APCs) act as vehicles that transfer HIV to their target CD4(+) cells through an intercellular junction, termed the virologic synapse. The molecules that are involved in this process remain largely unidentified. In this study, we used photoaffinity labeling and a proteomic approach to identify new proteins that facilitate HIV-1 transfer. We identified ectopic mitochondrial ATP synthase as a factor that mediates HIV-1 transfer between APCs and CD4(+) target cells. Monoclonal antibodies against the β-subunit of ATP synthase inhibited APC-mediated transfer of multiple strains HIV-1 to CD4(+) target cells. Likewise, the specific inhibitors of ATPase, citreoviridin and IF1, completely blocked APC-mediated transfer of HIV-1 at the APC-target cell interaction step. Confocal fluorescent microscopy showed localization of extracellular ATP synthase at junctions between APC and CD4(+) target cells. We conclude that ectopic ATP synthase could be an accessible molecular target for inhibiting HIV-1 proliferation in vivo.
authors: Membrane Structure and Function Section, Nanobiology Program, Center for Cancer Research, Bethesda, MD, USA.
authors: Amichai
authors: A
authors: Yavlovich
authors: Mathias
authors: M
authors: Viard
authors: Ming
authors: M
authors: Zhou
authors: Timothy D
authors: TD
authors: Veenstra
authors: Ji Ming
authors: JM
authors: Wang
authors: Wanghua
authors: W
authors: Gong
authors: Eliahu
authors: E
authors: Heldman
authors: Robert
authors: R
authors: Blumenthal
authors: Yossef
authors: Y
authors: Raviv
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D001692:Biological Transport / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007365:Intercellular Junctions / Q000276:immunology / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019920:Photoaffinity Labels / Q000494:pharmacology; D021381:Protein Transport / Q000276:immunology; D013194:Staining and Labeling / Q000379:methods; D014018:Tissue Distribution
chemical_list: C506526:ATP5F1B protein, human; D000906:Antibodies; D019920:Photoaffinity Labels; D025261:Mitochondrial Proton-Translocating ATPases