PLoS Biol. 10, e1001315 (2012)

Credit: PUBLIC LIBRARY OF SCIENCE

HIV-1 has evolved numerous strategies to promote viral transmission, including subverting the antiviral activity of these antigen-presenting cells of the immune system, dendritic cells (DCs). However, little is known about the molecular mechanisms underlying viral uptake by DCs. On the basis of previous work using glycosphingolipid biosynthesis inhibitors, Izquierdo-Useros et al. hypothesized that gangliosides on the outer monolayer of the viral membrane could act as viral attachment factors to allow recognition and capture by DCs. Captured viruses and lab-generated virus-like particles (VLPs) could then be transmitted to susceptible T cells in a process called trans-infection. To explore this idea, the authors showed that uptake of VLPs and of large unilamellar vesicles mimicking the size and lipid composition of HIV-1 required membrane gangliosides and involved similar trafficking within the DCs. Only gangliosides with exposed sialic acids attached to a lactose group (sialyllactose) could support uptake activity by DCs and facilitate subsequent viral trans-infection. These results demonstrate a new role for sialylated glycosphingolipids as new molecular recognition determinants for specific capture by DCs.