Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells

Nat Commun. 2014 Jun 20:5:4136. doi: 10.1038/ncomms5136.

Abstract

Ganglioside GM3, a host-derived glycosphingolipid incorporated in the membrane of human immunodeficiency virus-1 (HIV-1) viral particles, mediates interactions between HIV-1 and Siglec1/CD169, a protein expressed on dendritic cells (DCs). Such interactions, which seem to be independent of viral envelope glycoprotein gp120, are poorly understood. Here we develop a model system consisting of self-assembled artificial virus nanoparticles (AVNs) that are free of viral glycoproteins or other host-derived glycolipids and glycoproteins. These plasmonic AVNs contain a membrane of defined composition wrapped around a solid metal core. GM3-containing AVNs are captured by CD169-expressing HeLa cells or mature DCs, and are sequestered within non-lysosomal tetraspanin-positive compartments. This distribution is reminiscent of CD169-dependent HIV-1 sequestration in mature DCs. Our results highlight GM3-CD169 binding as a gp120-independent signal for sequestration and preservation of HIV-1 infectivity. They also indicate that plasmonic AVNs offer improved features over liposome-based systems and represent a versatile tool for probing specific virus-cell interactions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Primers / genetics
  • Dendritic Cells / metabolism*
  • G(M3) Ganglioside / metabolism*
  • HIV-1 / metabolism*
  • HeLa Cells
  • Humans
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Nanoparticles / metabolism*
  • Polymerase Chain Reaction
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism*
  • Spectrophotometry, Ultraviolet
  • Virus Internalization*

Substances

  • DNA Primers
  • G(M3) Ganglioside
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1