Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides

PLoS Biol. 2012;10(12):e1001448. doi: 10.1371/journal.pbio.1001448. Epub 2012 Dec 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Dendritic Cells / virology*
  • Exosomes / drug effects
  • Exosomes / metabolism
  • Gangliosides / metabolism*
  • Gene Silencing / drug effects
  • HEK293 Cells
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Immunological Synapses / drug effects
  • Lipid Bilayers / metabolism*
  • Lipopolysaccharides / pharmacology
  • Liposomes / metabolism
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism*
  • Up-Regulation / drug effects
  • Virion / drug effects
  • Virion / metabolism

Substances

  • Gangliosides
  • Lipid Bilayers
  • Lipopolysaccharides
  • Liposomes
  • Sialic Acid Binding Ig-like Lectin 1

Grant support

This work was supported by the Spanish Ministry of Science and Innovation through grant SAF2010-21224, the Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” (RD06/0006), the Catalan HIV Vaccine Development Program (HIVACAT), Gala contra la sida: Barcelona 2011, and by a grant from the Deutsche Forschungsgemeinschaft to H.-G.K. (TRR83; project 14). N.I-U. was supported by the program “José Castillejo” from the Spanish Ministry of Education. M.T.R.-P. is supported by grant BES-2008-002609 from the Spanish Ministry of Science and Innovation H.-G.K. is investigator of the Cell Networks Cluster of Excellence (EXC81). A.T. is supported by the Swiss National Science Foundation (31003A_132863). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.