title: 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.
authors.affiliation: Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Schiralli Lester
authors.forename: Hisashi
authors.initials: H
authors.lastname: Akiyama
authors.forename: Erica
authors.initials: E
authors.lastname: Evans
authors.forename: Juswinder
authors.initials: J
authors.lastname: Singh
authors.forename: Suryaram
authors.initials: S
authors.lastname: Gummuluru
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Henderson
mesh_terms: D000199:Actins / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D021962:Membrane Microdomains; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D019065:Virus Assembly; D057074:Virus Release; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D000199:Actins; D007376:Interleukin-2; D054301:gag Gene Products, Human Immunodeficiency Virus; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase