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

Yu X, Feizpour A, Ramirez NG, Wu L, Akiyama H, Xu F, Gummuluru S, Reinhard BM - Nat Commun (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, USA.

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.

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Strategies for AVN fabrication. Schematic overview of fabrication strategies S1 (top) for AVN1 and S2 (bottom) for AVN2. The encapsulation strategy S1 traps Au NPs in liposomes formed in situ, whereas in S2 pre-formed liposomes act as lipid reservoir for the assembly of lipid membranes around octadecanethiol coated Au NPs in a one-pot process. Abbreviations: Lipo = Liposome.
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Figure 2: Strategies for AVN fabrication. Schematic overview of fabrication strategies S1 (top) for AVN1 and S2 (bottom) for AVN2. The encapsulation strategy S1 traps Au NPs in liposomes formed in situ, whereas in S2 pre-formed liposomes act as lipid reservoir for the assembly of lipid membranes around octadecanethiol coated Au NPs in a one-pot process. Abbreviations: Lipo = Liposome.

Mentions: Different experimental strategies have been developed for creating lipid layers around NP cores with different sizes.23,45–49 For the relatively large NPs of our AVN design, two strategies in particular are promising (Fig. 2). Strategy 1 (S1) is based on a lipid encapsulation approach that traps Au NPs within unilamellar vesicles.46 Strategy 2 (S2) incorporates the lipids with their hydrophobic tail into an octadecane-thiol brush assembled on the surface of Au NPs.45 While S1 leads to a complete bilayer membrane, S2 embeds a single layer of lipids into a self-assembled monolayer of octadecane-thiols through their hydrophobic lipid tails. Both, S1 and S2, achieve a presentation of GM3 on the AVN surface with the sialic acid containing sugar head group pointing into the solution. In the following, we refer to the artificial virus nanoparticles obtained through these two strategies as AVN1 and AVN2, respectively. Although S2 is synthetically simpler and more efficient than S1, lipid mobility and density obtained via S2 are anticipated to differ from those of the native bilayer membrane of enveloped virus particles. A priori it was, therefore, unclear if AVN2 could successfully mimic virus-like-behavior and we consequently pursued and evaluated both strategies.


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

Yu X, Feizpour A, Ramirez NG, Wu L, Akiyama H, Xu F, Gummuluru S, Reinhard BM - Nat Commun (2014)

Strategies for AVN fabrication. Schematic overview of fabrication strategies S1 (top) for AVN1 and S2 (bottom) for AVN2. The encapsulation strategy S1 traps Au NPs in liposomes formed in situ, whereas in S2 pre-formed liposomes act as lipid reservoir for the assembly of lipid membranes around octadecanethiol coated Au NPs in a one-pot process. Abbreviations: Lipo = Liposome.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109413&req=5

Figure 2: Strategies for AVN fabrication. Schematic overview of fabrication strategies S1 (top) for AVN1 and S2 (bottom) for AVN2. The encapsulation strategy S1 traps Au NPs in liposomes formed in situ, whereas in S2 pre-formed liposomes act as lipid reservoir for the assembly of lipid membranes around octadecanethiol coated Au NPs in a one-pot process. Abbreviations: Lipo = Liposome.
Mentions: Different experimental strategies have been developed for creating lipid layers around NP cores with different sizes.23,45–49 For the relatively large NPs of our AVN design, two strategies in particular are promising (Fig. 2). Strategy 1 (S1) is based on a lipid encapsulation approach that traps Au NPs within unilamellar vesicles.46 Strategy 2 (S2) incorporates the lipids with their hydrophobic tail into an octadecane-thiol brush assembled on the surface of Au NPs.45 While S1 leads to a complete bilayer membrane, S2 embeds a single layer of lipids into a self-assembled monolayer of octadecane-thiols through their hydrophobic lipid tails. Both, S1 and S2, achieve a presentation of GM3 on the AVN surface with the sialic acid containing sugar head group pointing into the solution. In the following, we refer to the artificial virus nanoparticles obtained through these two strategies as AVN1 and AVN2, respectively. Although S2 is synthetically simpler and more efficient than S1, lipid mobility and density obtained via S2 are anticipated to differ from those of the native bilayer membrane of enveloped virus particles. A priori it was, therefore, unclear if AVN2 could successfully mimic virus-like-behavior and we consequently pursued and evaluated both strategies.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and The Photonics Center, Boston University, Boston, Massachusetts 02215, USA.

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.

Show MeSH
Related in: MedlinePlus