Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting cells to CD4(+) target cells

Blood. 2012 Aug 9;120(6):1246-53. doi: 10.1182/blood-2011-12-399063. Epub 2012 Jul 2.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antibodies / pharmacology
  • Antigen Presentation / physiology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Biological Transport / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • HEK293 Cells
  • HIV-1 / immunology
  • HIV-1 / metabolism*
  • HeLa Cells
  • Humans
  • Intercellular Junctions / immunology
  • Intercellular Junctions / metabolism
  • Mitochondrial Proton-Translocating ATPases / immunology
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Mitochondrial Proton-Translocating ATPases / physiology*
  • Photoaffinity Labels / pharmacology
  • Protein Transport / immunology
  • Staining and Labeling / methods
  • Tissue Distribution


  • ATP5F1B protein, human
  • Antibodies
  • Photoaffinity Labels
  • Mitochondrial Proton-Translocating ATPases