Interleukin 2-inducible T cell kinase (ITK) facilitates efficient egress of HIV-1 by coordinating Gag distribution and actin organization.

Abstract:

:Interleukin 2-inducible T cell kinase (ITK) influences T cell signaling by coordinating actin polymerization and polarization as well as recruitment of kinases and adapter proteins. ITK regulates multiple steps of HIV-1 replication, including virion assembly and release. Fluorescent microscopy was used to examine the functional interactions between ITK and HIV-1 Gag during viral particle release. ITK and Gag colocalized at the plasma membrane and were concentrated at sites of F-actin accumulation and membrane lipid rafts in HIV-1 infected T cells. There was polarized staining of ITK, Gag, and actin towards sites of T cell conjugates. Small molecule inhibitors of ITK disrupted F-actin capping, perturbed Gag-ITK colocalization, inhibited virus like particle release, and reduced HIV replication in primary human CD4+ T cells. These data provide insight as to how ITK influences HIV-1 replication and suggest that targeting host factors that regulate HIV-1 egress provides an innovative strategy for controlling HIV infection.

journal_name

Virology

journal_title

Virology

authors

Schiralli Lester GM,Akiyama H,Evans E,Singh J,Gummuluru S,Henderson AJ

doi

10.1016/j.virol.2012.11.015

subject

Has Abstract

pub_date

2013-02-05 00:00:00

pages

235-43

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(12)00575-2

journal_volume

436

pub_type

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