title: Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells.
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.
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Feizpour
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Nora-Guadalupe P
authors.initials: NG
authors.lastname: Ramirez
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Linxi
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Fangda
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Suryaram
authors.initials: S
authors.lastname: Gummuluru
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Björn M
authors.initials: BM
authors.lastname: Reinhard
mesh_terms: D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism*; D005679:G(M3) Ganglioside / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D053586:Virus Internalization
chemical_list: D017931:DNA Primers; D005679:G(M3) Ganglioside; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1