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

Richard L. Felts, Kedar Narayan, Jacob 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 journalArticle

126 Citations (Scopus)

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

Fingerprint

Synapses
Dendritic Cells
HIV
T-Lymphocytes
Virion
Viruses
HIV Receptors
Electron Microscope Tomography
Burial
CD4 Antigens
Membranes
Antigen-Presenting Cells
T-Cell Antigen Receptor
HIV Infections
Microscopy
Macrophages
Ions
Light

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells. / Felts, Richard L.; Narayan, Kedar; Estes, Jacob; Shi, Dan; Trubey, Charles M.; Fu, Jing; Hartnell, Lisa M.; Ruthel, Gordon T.; Schneider, Douglas K.; Nagashima, Kunio; Bess, Julian W.; Bavari, Sina; Lowekamp, Bradley C.; Bliss, Donald; Lifson, Jeffrey D.; Subramaniam, Sriram.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 30, 27.07.2010, p. 13336-13341.

Research output: Contribution to journalArticle

Felts, RL, Narayan, K, Estes, J, Shi, D, Trubey, CM, Fu, J, Hartnell, LM, Ruthel, GT, Schneider, DK, Nagashima, K, Bess, JW, Bavari, S, Lowekamp, BC, Bliss, D, Lifson, JD & Subramaniam, S 2010, '3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 30, pp. 13336-13341. https://doi.org/10.1073/pnas.1003040107
Felts, Richard L. ; Narayan, Kedar ; Estes, Jacob ; Shi, Dan ; Trubey, Charles M. ; Fu, Jing ; Hartnell, Lisa M. ; Ruthel, Gordon T. ; Schneider, Douglas K. ; Nagashima, Kunio ; Bess, Julian W. ; Bavari, Sina ; Lowekamp, Bradley C. ; Bliss, Donald ; Lifson, Jeffrey D. ; Subramaniam, Sriram. / 3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 30. pp. 13336-13341.
@article{62259d6f83c247669e80aa9c1c63dc1c,
title = "3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells",
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.",
keywords = "3D imaging, Cell-cell contact, Electron tomography, Neutralizing antibodies, Viral entry",
author = "Felts, {Richard L.} and Kedar Narayan and Jacob Estes and Dan Shi and Trubey, {Charles M.} and Jing Fu and Hartnell, {Lisa M.} and Ruthel, {Gordon T.} and Schneider, {Douglas K.} and Kunio Nagashima and Bess, {Julian W.} and Sina Bavari and Lowekamp, {Bradley C.} and Donald Bliss and Lifson, {Jeffrey D.} and Sriram Subramaniam",
year = "2010",
month = "7",
day = "27",
doi = "10.1073/pnas.1003040107",
language = "English (US)",
volume = "107",
pages = "13336--13341",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "30",

}

TY - JOUR

T1 - 3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

AU - Felts, Richard L.

AU - Narayan, Kedar

AU - Estes, Jacob

AU - Shi, Dan

AU - Trubey, Charles M.

AU - Fu, Jing

AU - Hartnell, Lisa M.

AU - Ruthel, Gordon T.

AU - Schneider, Douglas K.

AU - Nagashima, Kunio

AU - Bess, Julian W.

AU - Bavari, Sina

AU - Lowekamp, Bradley C.

AU - Bliss, Donald

AU - Lifson, Jeffrey D.

AU - Subramaniam, Sriram

PY - 2010/7/27

Y1 - 2010/7/27

N2 - 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.

AB - 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.

KW - 3D imaging

KW - Cell-cell contact

KW - Electron tomography

KW - Neutralizing antibodies

KW - Viral entry

UR - http://www.scopus.com/inward/record.url?scp=77955781209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955781209&partnerID=8YFLogxK

U2 - 10.1073/pnas.1003040107

DO - 10.1073/pnas.1003040107

M3 - Article

C2 - 20624966

AN - SCOPUS:77955781209

VL - 107

SP - 13336

EP - 13341

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 30

ER -