TY - JOUR
T1 - Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides
AU - Izquierdo-Useros, Nuria
AU - Lorizate, Maier
AU - Puertas, Maria C.
AU - Rodriguez-Plata, Maria T.
AU - Zangger, Nadine
AU - Erikson, Elina
AU - Pino, Maria
AU - Erkizia, Itziar
AU - Glass, Bärbel
AU - Clotet, Bonaventura
AU - Keppler, Oliver T.
AU - Telenti, Amalio
AU - Kräusslich, Hans Georg
AU - Martinez-Picado, Javier
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pbio.1001448
DO - 10.1371/journal.pbio.1001448
M3 - Article
SN - 1544-9173
VL - 10
JO - PLoS Biology
JF - PLoS Biology
IS - 12
M1 - e1001448
ER -