Quantitative 3D video microscopy of HIV transfer across T cell virological synapses

Science. 2009 Mar 27;323(5922):1743-7. doi: 10.1126/science.1167525.


The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV across the virological synapse. Quantitative, high-speed three-dimensional (3D) video microscopy revealed the rapid formation of micrometer-sized "buttons" containing oligomerized viral Gag protein. Electron microscopy showed that these buttons were packed with budding viral crescents. Viral transfer events were observed to form virus-laden internal compartments within target cells. Continuous time-lapse monitoring showed preferential infection through synapses. Thus, HIV dissemination may be enhanced by virological synapse-mediated cell adhesion coupled to viral endocytosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes / physiology*
  • CD4-Positive T-Lymphocytes / ultrastructure
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Adhesion*
  • Coculture Techniques
  • Cytochalasin D / pharmacology
  • Endocytosis
  • HIV / physiology*
  • HIV / ultrastructure
  • Humans
  • Imaging, Three-Dimensional
  • Jurkat Cells
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Microscopy, Video
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Virus Internalization*
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*


  • CXCR4 protein, human
  • Receptors, CCR5
  • Receptors, CXCR4
  • Recombinant Fusion Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • Cytochalasin D