PI4P5-kinase Iα is required for efficient HIV-1 entry and infection of T cells
| Autor: | Francisco Sánchez-Madrid, José Román Cabrero, Susana Álvarez-Losada, Jonathan Barroso-González, Mónica Gordón-Alonso, María Ángeles Muñoz-Fernández, Agustín Valenzuela-Fernández, Marta Barrero-Villar |
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| Předmět: |
Phosphatidylinositol 4
5-Diphosphate T-Lymphocytes Immunology Cell Mutant Blotting Western Fluorescent Antibody Technique Biology HIV Envelope Protein gp120 Virus chemistry.chemical_compound Cell Line Tumor medicine Immunology and Allergy Humans Phosphatidylinositol Gene knockdown Microscopy Confocal Kinase virus diseases Lipid bilayer fusion Cell biology Phosphotransferases (Alcohol Group Acceptor) medicine.anatomical_structure Viral replication chemistry HIV-1 |
| Zdroj: | Scopus-Elsevier |
| Popis: | HIV-1 envelope (Env) triggers membrane fusion between the virus and the target cell. The cellular mechanism underlying this process is not well known. Phosphatidylinositol 4,5-bisphosphate (PIP2) is known to be important for the late steps of the HIV-1 infection cycle by promoting Gag localization to the plasma membrane during viral assembly, but it has not been implicated in early stages of HIV-1 membrane-related events. In this study, we show that binding of the initial HIV-1 Env-gp120 protein induces PIP2 production in permissive lymphocytes through the activation of phosphatidylinositol-4-phosphate 5-kinase (PI4P5-K) Iα. Overexpression of wild-type PI4P5-K Iα increased HIV-1 Env-mediated PIP2 production and enhanced viral replication in primary 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 Iα. Similar results were obtained with replicative and single-cycle HIV-1 particles. HIV-1 infection was also inhibited by knockdown of endogenous expression of PI4P5-K Iα. These data indicate that PI4P5-K Iα-mediated PIP2 production is crucial for HIV-1 entry and the early steps of infection in permissive lymphocytes. |
| Databáze: | OpenAIRE |
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