The regulated secretory pathway in cd4 + t cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse

Direct cell-cell spread of human immunodeficiency virus type-1 (hiv-1) at the virological synapse (vs) is an efficient mode of dissemination between cd4 + t cells but the mechanisms by which hiv-1 proteins are directed towards intercellular contacts is unclear. we have used confocal microscopy and electron tomography coupled with functional virology and cell biology of primary cd4 + t cells from normal individuals and patients with chediak-higashi syndrome and report that the hiv-1 vs displays a regulated secretion phenotype that shares features with polarized secretion at the t cell immunological synapse (is). cell-cell contact at the vs re-orientates the microtubule organizing center (mtoc) and organelles within the hiv-1-infected t cell towards the engaged target t cell,concomitant with polarization of viral proteins. directed secretion of proteins at the t cell is requires specialized organelles termed secretory lysosomes (sl) and we show that the hiv-1 envelope glycoprotein (env) localizes with ctla-4 and fasl in sl-related compartments and at the vs. finally,cd4 + t cells that are disabled for regulated secretion are less able to support productive cell-to-cell hiv-1 spread. we propose that hiv-1 hijacks the regulated secretory pathway of cd4 + t cells to enhance its dissemination. © 2011 jolly et al.