Although human dendritic cells (DCs) are largely resistant to productive infection with human immunodeficiency virus type 1 (HIV-1), they efficiently transmit the virus to T cells through a process called 'trans-infection'. In Cell, Ménager and Littman screen human monocyte-derived DCs with short hairpin RNA and identify the membrane protein TSPAN7 and the actin nucleator DNM2 as regulators of T cell trans-infection. TSPN7-deficient DCs show loss of dendrites, while both DNM2- as well as TSPN7-deficient DCs show redistribution of HIV-1 particles to the cytoplasmic compartment, increased HIV-1 localization in micropinosomes and reduced trans-infection. Inhibition of endocytosis and macropinocytosis or restoration of HIV-1 localization on dendrites enhances trans-infection. These results indicate that the internalization of HIV-1 by DCs through various mechanisms diminishes its transfer to T cells.

Cell 164, 695–709 (2016)