RT info:eu-repo/semantics/article
T1 PI4P5-Kinase Ialpha Is Required for Efficient HIV-1 Entry and Infection of T Cells.
A1 Valenzuela Fernández, Agustín
A1 Barrero Villar, Marta
A1 Barroso Gonza´lez, Jonathan
A1 Cabrero, J. R.
A1 Gordón Alonso, Mónica
A1 Álvarez Losada, Susana
A1 Muñoz Fernández, M. A.
A1 Sánchez Madrid, Francisco
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral".
AB HIV-1 envelope (Env) triggers membrane fusion between the virus and the target cell. The cellular mechanism underlying thisprocess is not well known. Phosphatidylinositol 4,5-bisphosphate (PIP2) is known to be important for the late steps of the HIV-1infection cycle by promoting Gag localization to the plasma membrane during viral assembly, but it has not been implicated inearly stages of HIV-1 membrane-related events. In this study, we show that binding of the initial HIV-1 Env-gp120 protein inducesPIP2 production in permissive lymphocytes through the activation of phosphatidylinositol-4-phosphate 5-kinase (PI4P5-K) I!.Overexpression of wild-type PI4P5-K I! increased HIV-1 Env-mediated PIP2 production and enhanced viral replication inprimary lymphocytes and CEM T cells, whereas PIP2 production and HIV-1 infection were both severely reduced in cells overexpressing the kinase-dead mutant D227A (D/A)-PI4P5-K I!. Similar results were obtained with replicative and single-cycle HIV-1particles. HIV-1 infection was also inhibited by knockdown of endogenous expression of PI4P5-K I!. These data indicate that PI4P5-KI!-mediated PIP2 production is crucial for HIV-1 entry and the early steps of infection in permissive lymphocytes
YR 2008
FD 2008
LK http://riull.ull.es/xmlui/handle/915/35356
UL http://riull.ull.es/xmlui/handle/915/35356
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 18-may-2024