RAB27A CONTROL HIV ASSEMBLY IN MACROPHAGES AND CD4 T CELLS

MATIAS OSTROWSKI

Los Cocos, Cordoba

Congreso; LXI Reunion Anual de la Sociedad Argentina de Inmunologia; 2013

Sociedad Argentina de Inmunologia

During the late stages of the HIV-1 replication cycle, the viral polyprotein 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.