Rab27a controla el tráfico de Gag y el ensamblado del VIH en macrófagos y linfocitos T CD4+.

MATIAS OSTROWSKI

Maintencillo

Congreso; XXXV Congreso Chileno de Microbiología; 2013

Sociedad Chilena de Microbiologia

During the late stages of the HIV-1 replication cycle, Gag is recruited to the plasma membrane (PM), where it directs HIV-1 assembly. Here, we demonstrate that the small GTPase Rab27a controls membrane association of Gag, both in primary macrophages and CD4+T lymphocytes, the main targets of HIV-1 infection. In the absence of Rab27a, the levels of phosphatidylinositol-(4,5)-biphosphate [PI(4,5)P2] at the PM are decreased. Consequently, Gag remains cytosolic and viral assembly is impaired. The establishment of virological synapses and viral transmission at points of cell-cell contacts also require functional Rab27a. To further characterize the role of Rab27a, we performed an shRNA screening targeting Rab27a effectors. We show that the knock-down of Slp2a, Slp3 and Slac2b phenocopies that of Rab27a, regulating Gag association with the PM and viral production. We conclude that during infection, Rab27a and three of its effectors control the levels of PI(4,5)P2 at the PM, thereby determining the recruitment of Gag and HIV-1 assembly.