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Type I phosphatidylinositol-4-phosphate 5-kinase α and γ play a key role in targeting HIV-1 Pr55(Gag) to the plasma membrane

Item Type:Article
Title:Type I phosphatidylinositol-4-phosphate 5-kinase α and γ play a key role in targeting HIV-1 Pr55(Gag) to the plasma membrane
Creators Name:Gonzales, B. and de Rocquigny, H. and Beziau, A. and Durand, S. and Burlaud-Gaillard, J. and Lefebvre, A. and Krull, S. and Emond, P. and Brand, D. and Piver, E.
Abstract:HIV-1 assembly occurs principally at the plasma membrane (PM) of infected cells. Gag polyprotein precursors (Pr55(Gag)) are targeted to the PM and their binding is mediated by the interaction of myristoylated matrix domain and a PM-specific phosphoinositide, the phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P(2)). The major synthesis pathway of PI(4,5)P(2) involves the activity of phosphatidylinositol 4-phosphate 5-kinase family type 1 composed of three isoforms (PIP5K1α, β and γ). To examine whether the activity of a specific PIP5K1 isoform determines proper Pr55(Gag) localization at the PM, we compared cellular behavior of Pr55(Gag) in the context of PIP5K1 inhibition using siRNAs that individually targeted each of the three isoforms in TZM-bl HeLa cells. We found that downregulation of PIP5K1α and PIP5K1γ strongly impaired the targeting of Pr55Gag to the PM with a rerouting of the polyprotein within intracellular compartments. The efficiency of Pr55(Gag) release was thus impaired through the silencing of these two isoforms while PIP5K1β is dispensable for Pr55(Gag) targeting to PM. The PM-mistargeting due to the silencing of PIP5K1α leads to Pr55(Gag) hydrolysis through lysosome and proteasome pathways while the silencing of PIP5K1γ leads to Pr55(Gag) accumulation in late endosomes. Our findings demonstrated that, within the PIP5K1s family, only the PI(4,5)P(2) pools produced by PIP5K1α and γ are involved in Pr55(Gag) PM targeting process.
Keywords:HIV-1, PIP5K1, Pr55(Gag)
Source:Journal of Virology
Publisher:American Society for Microbiology
Page Range:e00189
Date:1 July 2020
Additional Information:Copyright © 2020 American Society for Microbiology. All Rights Reserved.
Official Publication:https://doi.org/10.1128/JVI.00189-20
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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