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

Wolfgang Hübner; Gregory P. McNerney; Ping Chen; Benjamin M. Dale; Ronald E. Gordon; Frank Chuang; Xiao Dong Li; David Asmuth; Thomas R Huser; Benjamin K. Chen

doi:10.1126/science.1167525

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

Wolfgang Hübner, Gregory P. McNerney, Ping Chen, Benjamin M. Dale, Ronald E. Gordon, Frank Chuang, Xiao Dong Li, David Asmuth, Thomas R Huser, Benjamin K. Chen

Research output: Contribution to journal › Article

314 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1743-1747
Number of pages	5
Journal	Science
Volume	323
Issue number	5922
DOIs	https://doi.org/10.1126/science.1167525
State	Published - Mar 27 2009

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Hübner, W., McNerney, G. P., Chen, P., Dale, B. M., Gordon, R. E., Chuang, F., Li, X. D., Asmuth, D., Huser, T. R., & Chen, B. K. (2009). Quantitative 3D video microscopy of HIV transfer across T cell virological synapses. Science, 323(5922), 1743-1747. https://doi.org/10.1126/science.1167525

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AU - Hübner, Wolfgang

AU - McNerney, Gregory P.

AU - Chen, Ping

AU - Dale, Benjamin M.

AU - Gordon, Ronald E.

AU - Chuang, Frank

AU - Li, Xiao Dong

AU - Asmuth, David

AU - Huser, Thomas R

AU - Chen, Benjamin K.

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AB - 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.

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10.1126/science.1167525