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Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.

ABSTRACT: Next-generation nanoparticle-based drug delivery systems require the ability to target specific organelles or subcellular regions in selected target cells. Human immunodeficiency virus type I (HIV-1) particles are evolutionarily optimized nanocarriers that have evolved to avoid intracellular degradation and achieve enrichment at the synapse between mature dendritic cells (mDCs) and T cells by subverting cellular trafficking mechanisms. This study demonstrates that integration of the glycosphingolipid, GM3, in a membrane around a solid nanoparticle (NP) core is sufficient to recapitulate key aspects of the virus particle trafficking in mDCs. GM3-presenting artificial virus NPs (GM3-AVNs) accumulate in CD169(+) and CD81(+) nonlysosomal compartments in an actin-dependent process that mimics the sequestration of HIV-1. Live-cell optical tracking studies reveal a preferential recruitment and arrest of surface scanning CD4(+) T cells in direct vicinity to the AVN-enriched compartments. The formed mDC-T cell conjugates exhibit strong morphological similarities between the GM3-AVN-containing mDC-T cell synapse and the HIV-1 virological synapse, indicating that GM3-CD169 interactions alone are sufficient for establishing the mDC-T cell virological synapse. These results emphasize the potential of the GM3-AVN approach for providing therapeutic access to a key step of the host immune response--formation of the synaptic junction between an antigen-presenting cell (mDC) and T cells--for modulating and controlling immune responses.

SUBMITTER: Yu X

PROVIDER: S-EPMC4423798 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.

Yu Xinwei X Xu Fangda F Ramirez Nora-Guadalupe P NG Kijewski Suzanne D G SD Akiyama Hisashi H Gummuluru Suryaram S Reinhard Björn M BM

ACS nano 20150414 4

Next-generation nanoparticle-based drug delivery systems require the ability to target specific organelles or subcellular regions in selected target cells. Human immunodeficiency virus type I (HIV-1) particles are evolutionarily optimized nanocarriers that have evolved to avoid intracellular degradation and achieve enrichment at the synapse between mature dendritic cells (mDCs) and T cells by subverting cellular trafficking mechanisms. This study demonstrates that integration of the glycosphingo ...[more]

PMID: 25853367

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Dataset Information

Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.

Publications

Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.

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