RAB27A CONTROLS HIV ASSEMBLY IN MACROPHAGES AND CD4 T CELLS

OSTROWSKI, MATIAS

Girona

Conferencia; Gordon Research Conference. Viruses and Cells; 2015

Gordon Research Conferences

During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55 Gag is recruited to the plasma membrane (PM), where it binds phospha-tidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 toward 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, therefore controlling Pr55 Gag membrane association. Rab27a also controls PI(4,5)P2levels at the virus-containing com-partments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55 Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KII alpha to the PM. We conclude that by directing the trafficking of PI4KII alpha-positive endosomes toward the PM, Rab27a controls PI(4,5)P2production and, consequently, HIV-1 replication.