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

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 unc...

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Egile Nagusiak: Martin, N, Welsch, S, Jolly, C, Briggs, J, Vaux, D, Sattentau, Q
Formatua: Journal article
Hizkuntza:English
Argitaratua: 2010
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author Martin, N
Welsch, S
Jolly, C
Briggs, J
Vaux, D
Sattentau, Q
author_facet Martin, N
Welsch, S
Jolly, C
Briggs, J
Vaux, D
Sattentau, Q
author_sort Martin, N
collection OXFORD
description 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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spelling oxford-uuid:c15fd23b-779c-40c0-9af8-58c0a6d03e792022-03-27T06:01:03ZVirological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c15fd23b-779c-40c0-9af8-58c0a6d03e79EnglishSymplectic Elements at Oxford2010Martin, NWelsch, SJolly, CBriggs, JVaux, DSattentau, QHuman 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.
spellingShingle Martin, N
Welsch, S
Jolly, C
Briggs, J
Vaux, D
Sattentau, Q
Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.
title Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.
title_full Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.
title_fullStr Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.
title_full_unstemmed Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.
title_short Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.
title_sort virological synapse mediated spread of human immunodeficiency virus type 1 between t cells is sensitive to entry inhibition
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