Interferon-Inducible Mechanism of Dendritic Cell-Mediated HIV-1 Dissemination Is Dependent on Siglec-1/CD169

Human immunodeficiency virus type 1 (hiv-1) interactions with myeloid dendritic cells (dcs) can result in virus dissemination to cd4+ t cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (gsl),gm3. the mechanism of dc-mediated trans infection is extremely efficacious and can result in infection of multiple cd4+ t cells as these cells make exploratory contacts on the dc surface. while it has long been appreciated that activation of dcs with ligands that induce type i ifn signaling pathway dramatically enhances dc-mediated t cell trans infection,the mechanism by which this occurs has remained unclear until now. here,we demonstrate that the type i ifn-inducible siglec-1,cd169,is the dc receptor that captures hiv in a gm3-dependent manner. selective downregulation of cd169 expression,neutralizing cd169 function,or depletion of gsls from virions,abrogated dc-mediated hiv-1 capture and trans infection,while exogenous expression of cd169 in receptor-naïve cells rescued gsl-dependent capture and trans infection. hiv-1 particles co-localized with cd169 on dc surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the dc - t cell infectious synapses upon initiation of t cell contact. together,these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (gm3 - cd169 interaction) for dc-dependent hiv dissemination. © 2013 puryear et al.