3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

Richard L. Felts, Kedar Narayan, Jacob D. Estes, Dan Shi, Charles M. Trubey, Jing Fu, Lisa M. Hartnell, Gordon T. Ruthel, Douglas K. Schneider, Kunio Nagashima, Julian W. Bess, Sina Bavari, Bradley C. Lowekamp, Donald Bliss, Jeffrey D. Lifson, Sriram Subramaniam

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

Abstract

The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4+ T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial extensions emanating from CD4+ T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer by T cells highlight unique aspects of cell-cell HIV transmission.

Original languageEnglish (US)
Pages (from-to)13336-13341
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number30
DOIs
StatePublished - Jul 27 2010
Externally publishedYes

Keywords

  • 3D imaging
  • Cell-cell contact
  • Electron tomography
  • Neutralizing antibodies
  • Viral entry

ASJC Scopus subject areas

  • General

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