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

Hübner, Wolfgang; McNerney, Gregory P; Chen, Ping; Dale, Benjamin M; Gordon, Ronald E; Chuang, Frank Y S; Li, Xiao-Dong; Asmuth, David M et al. · Science · 2009

basic_science · Level V

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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.

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