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HIV envelope-mediated, CCR5/?4?7-dependent killing of CD4-negative ?? T cells which are lost during progression to AIDS.

ABSTRACT: HIV infects and replicates in CD4+ T cells but effects on host immunity and disease also involve depletion, hyper-activation, and modification of CD4-negative cell populations. In particular, the depletion of CD4-negative ?? T cells is common to all HIV+ individuals. We found that soluble or cell-associated envelope glycoproteins from CCR5-tropic strains of HIV could bind, activates the p38-caspase pathway, and induce the death of ?? cells. Envelope binding requires integrin ?4?7 and chemokine receptor CCR5 which are at high levels and form a complex on the ?? T cell membrane. This receptor complex facilitated V3 loop binding to CCR5 in the absence of CD4-induced conformational changes. Cell death was increased by antigen stimulation after exposure to envelope glycoprotein. Direct signaling by envelope glycoprotein killed CD4-negative ?? T cells and reproduced a defect observed in all patients with HIV disease.

SUBMITTER: Li H

PROVIDER: S-EPMC3228498 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative γδ T cells which are lost during progression to AIDS.

Li Haishan H Pauza C David CD

Blood 20110916 22

HIV infects and replicates in CD4+ T cells but effects on host immunity and disease also involve depletion, hyper-activation, and modification of CD4-negative cell populations. In particular, the depletion of CD4-negative γδ T cells is common to all HIV+ individuals. We found that soluble or cell-associated envelope glycoproteins from CCR5-tropic strains of HIV could bind, activates the p38-caspase pathway, and induce the death of γδ cells. Envelope binding requires integrin α4β7 and chemokine r ...[more]

PMID: 21926353

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