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

Publication ,  Journal Article
Yu, X; Xu, F; Ramirez, N-GP; Kijewski, SDG; Akiyama, H; Gummuluru, S; Reinhard, BM
Published in: ACS nano
January 2015

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.

Duke Scholars

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Published In

ACS nano

DOI

EISSN

1936-086X

ISSN

1936-0851

Publication Date

January 2015

Volume

9

Issue

4

Start / End Page

4182 / 4192

Related Subject Headings

  • Virion
  • T-Lymphocytes
  • Signal Transduction
  • Sialic Acid Binding Ig-like Lectin 1
  • Nanoscience & Nanotechnology
  • Metal Nanoparticles
  • Immunological Synapses
  • Humans
  • HIV-1
  • Gold
 

Citation

APA
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ICMJE
MLA
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Yu, X., Xu, F., Ramirez, N.-G., Kijewski, S. D. G., Akiyama, H., Gummuluru, S., & Reinhard, B. M. (2015). Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse. ACS Nano, 9(4), 4182–4192. https://doi.org/10.1021/acsnano.5b00415
Yu, Xinwei, Fangda Xu, Nora-Guadalupe P. Ramirez, Suzanne D. G. Kijewski, Hisashi Akiyama, Suryaram Gummuluru, and Björn M. Reinhard. “Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.ACS Nano 9, no. 4 (January 2015): 4182–92. https://doi.org/10.1021/acsnano.5b00415.
Yu X, Xu F, Ramirez N-GP, Kijewski SDG, Akiyama H, Gummuluru S, et al. Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse. ACS nano. 2015 Jan;9(4):4182–92.
Yu, Xinwei, et al. “Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.ACS Nano, vol. 9, no. 4, Jan. 2015, pp. 4182–92. Epmc, doi:10.1021/acsnano.5b00415.
Yu X, Xu F, Ramirez N-GP, Kijewski SDG, Akiyama H, Gummuluru S, Reinhard BM. Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse. ACS nano. 2015 Jan;9(4):4182–4192.
Journal cover image

Published In

ACS nano

DOI

EISSN

1936-086X

ISSN

1936-0851

Publication Date

January 2015

Volume

9

Issue

4

Start / End Page

4182 / 4192

Related Subject Headings

  • Virion
  • T-Lymphocytes
  • Signal Transduction
  • Sialic Acid Binding Ig-like Lectin 1
  • Nanoscience & Nanotechnology
  • Metal Nanoparticles
  • Immunological Synapses
  • Humans
  • HIV-1
  • Gold