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Imaging of HIV-1 Envelope-induced Virological Synapse and Signaling on Synthetic Lipid Bilayers
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Published on: March 8, 2012

Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry

Nicola Martin1, Sonja Welsch, Clare Jolly

  • 1Department of Pathology, The University of Oxford, South Parks Road, Oxford OX1 3R, United Kingdom.

Journal of Virology
|January 22, 2010
PubMed

Human immunodeficiency virus type 1 (HIV-1) can disseminate between CD4(+) T cells via diffusion-limited cell-free viral spread or by directed cell-cell transfer using virally induced structures termed virological synapses. Although T-cell virological synapses have been well characterized, it is unclear whether this mode of viral spread is susceptible to inhibition by neutralizing antibodies and entry inhibitors. We show here that both cell-cell and cell-free viral spread are equivalently sensitive to entry inhibition. Fluorescence imaging analysis measuring virological synapse lifetimes and inhibitor time-of-addition studies implied that inhibitors can access preformed virological synapses and interfere with HIV-1 cell-cell infection. This concept was supported by electron tomography that revealed the T-cell virological synapse to be a relatively permeable structure. Virological synapse-mediated HIV-1 spread is thus efficient but is not an immune or entry inhibitor evasion mechanism, a result that is encouraging for vaccine and drug design.

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