Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides

Dendritic cells (dcs) are essential antigen-presenting cells for the induction of immunity against pathogens. however,hiv-1 spread is strongly enhanced in clusters of dcs and cd4+ t cells. uninfected dcs capture hiv-1 and mediate viral transfer to bystander cd4+ t cells through a process termed trans-infection. initial studies identified the c-type lectin dc-sign as the hiv-1 binding factor on dcs,which interacts with the viral envelope glycoproteins. upon dc maturation,however,dc-sign is down-regulated,while hiv-1 capture and trans-infection is strongly enhanced via a glycoprotein-independent capture pathway that recognizes sialyllactose-containing membrane gangliosides. here we show that the sialic acid-binding ig-like lectin 1 (siglec-1,cd169),which is highly expressed on mature dcs,specifically binds hiv-1 and vesicles carrying sialyllactose. furthermore,siglec-1 is essential for trans-infection by mature dcs. these findings identify siglec-1 as a key factor for hiv-1 spread via infectious dc/t-cell synapses,highlighting a novel mechanism that mediates hiv-1 dissemination in activated tissues. © 2012 izquierdo-useros et al.