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
Virologyjournal_title
Virologyauthors
Schiralli Lester GM,Akiyama H,Evans E,Singh J,Gummuluru S,Henderson AJdoi
10.1016/j.virol.2012.11.015subject
Has Abstractpub_date
2013-02-05 00:00:00pages
235-43issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(12)00575-2journal_volume
436pub_type
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