Identification of Host Trafficking Genes Required for HIV-1 Virological Synapse Formation in Dendritic Cells

Abstract

The lentivirus human immunodeficiency virus (HIV) targets and destroys CD4 + T cells, leaving the host vulnerable to life-threatening opportunistic infections associated with AIDS. Dendritic cells (DCs) form a virological synapse (VS) with CD4 + T cells, enabling the efficient transfer of virus between the two cells. We have identified cellular factors that are critical in the induction of the VS. We show that ADP-ribosylation factor 1 (ARF1), bridging integrator 1 (BIN1), and Rab GTPases RAB7L1 and RAB8A are important regulators of HIV-1 trafficking to the VS and therefore the infection of CD4 + T cells. We found these cellular factors were essential for endosomal protein trafficking and formation of the VS and that depletion of target proteins prevented virus trafficking to the plasma membrane by retaining virus in intracellular vesicles. Identification of key regulators in HIV-1 trans -infection between DC and CD4 + T cells has the potential for the development of targeted therapy to reduce trans -infection of HIV-1 in vivo .