Rab27a Controls HIV-1 Gag Trafficking and Virus Assembly by regulating Plasma Membrane levels of PI(4,5)P2

PEHUÉN PEREYRA GERBER; MERCEDES CABRINI; CAROLINA JANCIC; LUCIANA PAOLETTI; CLAUDIA BANCHIO; CATALINA VON BILDERING; LORENA SIGAUT; LÍA ISABEL PIETRASANTA; GABRIEL DUETTE; ERIC O. FREED; GENEVIEVE DE SAINT BASILE; CATARINA FERREIRA MOITA; LUIS FERREIRA MOITA; SEBASTIAN AMIGORENA; PHILIPPE BENAROCH; JORGE GEFFNER; MATÍAS OSTROWSKI

JOURNAL OF CELL BIOLOGY

ROCKEFELLER UNIV PRESS

Lugar: New York; Año: 2015

0021-9525

During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and directs HIV-1 assembly. We demonstrate that the small GTPase Rab27a regulates Pr55Gag membrane association, both in primary macrophages and CD4+T cells, thus controlling viral assembly and replication. We show that Rab27a controls the trafficking of multivesicular endosomes (MVEs) carrying phosphatidylinositol 4-kinase type 2 alpha (PI4KII) towards the PM of CD4+ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, controlling the formation of the HIV-1 assembly platform. Rab27a also controls PI(4,5)P2 levels at the Virus-Containing Compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3 and Slac2b are required for the association of Pr55Gag with the PM. We conclude that by directing the trafficking of PI4KII-positive endosomes towards the PM, Rab27a controls PI(4,5)P2 levels and HIV-1 replication.