Adhesion Molecule Interactions Facilitate Human Immunodeficiency Virus Type 1-Induced Virological Synapse Formation between T Cells

Jolly, Clare; Mitar, Ivonne; Sattentau, Quentin J.

doi:10.1128/jvi.01585-07

Cited by 153 publications

(210 citation statements)

References 35 publications

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“…They also result in trapping of the contents of the adjacent aqueous environment and material bound to the cell surface, including virions when present, in compartments that are essentially surface membrane invaginations. At the regions of local contact between dendritic cells and T cells, virion-rich compartments are predominantly localized toward the T-cell interface, presumably in an actin-dependent process (31), with cell-cell contact mediated by cell surface adhesion molecules (32). This model is also consistent with the evidence that HIV-1 alters endolysosomal traffic in dendritic cells (33), although virions themselves appear not to be present in endolysosomes.…”

Section: Discussionsupporting

confidence: 77%

“…In the absence of CD4 availability on the T cell or when gp120 on the viral surface is prevented from binding CD4, the viruses remain associated with the dendritic cell, perhaps via interactions with dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) (35,36) (other receptors are possible) until the formation of productive synapses with T cells that are capable of supporting gp120-CD4 interaction. We note that virological synapses between T cells alone have also been described (7,32,37), and the available data suggest that these synapses may be less complex and devoid of the large membrane encasement reported here with mature dendritic cells.…”

Section: Discussionmentioning

confidence: 93%

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

Felts

Narayan

Estes

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

175

176

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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.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 93%

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

Felts

Narayan

Estes

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

175

176

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“…At any rate, the plasma membrane is what the virus particle encounters first. Thus, the spatial organization of transmembrane proteins at the cell surface and the physical state of the lipid bilayer are critical regulators of HIV-1 entry (11,14,15,18,(53)(54)(55). Supporting this statement, there is an increasing number of studies showing that cellular proteins affecting either the clustering of viral receptors (such as tetraspanins, EWI-2, moesin, and filamin-A) or the subcortical actin cytoskeleton (such as syntenin-1, ␣-actinin, talin, vinculin, cofilin, profilin, WASp, WAVE-2, diaphanous-2, and Arp2/3) alter HIV-1 infection effectiveness (15, 18, 20, 24, 26, 30, 31, 56 -60).…”

Section: Discussionmentioning

confidence: 99%

Actin-binding Protein Drebrin Regulates HIV-1-triggered Actin Polymerization and Viral Infection

Gordon-Alonso

Rocha-Perugini

Álvarez

et al. 2013

Journal of Biological Chemistry

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Background: Drebrin binds to F-actin and CXCR4 in T cells. Thus, it is a potential candidate for the modulation of HIV-1 infection. Results: Drebrin and CXCR4 accumulate at viral attachment areas. Drebrin knockdown decreases F-actin polymerization, and increases local profilin accumulation and HIV-1 infection. Conclusion: Drebrin inhibits HIV-1 entry by stabilizing HIV-1-triggered F-actin polymerization. Significance: Modulation of actin dynamics differentially regulates each viral step for an effective viral infection. HIV-1 contact with target cells triggers F-actin rearrangements that are essential for several steps of the viral cycle. Successful HIV entry into CD4؉ T cells requires actin reorganization induced by the interaction of the cellular receptor/co-receptor complex CD4/CXCR4 with the viral envelope complex gp120/gp41 (Env).In this report, we analyze the role of the actin modulator drebrin in HIV-1 viral infection and cell to cell fusion. We show that drebrin associates with CXCR4 before and during HIV infection. Drebrin is actively recruited toward cellvirus and Env-driven cell to cell contacts. After viral internalization, drebrin clustering is retained in a fraction of the internalized particles. Through a combination of RNAi-based inhibition of endogenous drebrin and GFP-tagged expression of wild-type and mutant forms, we establish drebrin as a negative regulator of HIV entry and HIV-mediated cell fusion. Down-regulation of drebrin expression promotes HIV-1 entry, decreases F-actin polymerization, and enhances profilin local accumulation in response to HIV-1. These data underscore the negative role of drebrin in HIV infection by modulating viral entry, mainly through the control of actin cytoskeleton polymerization in response to HIV-1.Human immunodeficiency virus (HIV)-1 entry requires fusion between the viral envelope and the plasma membrane of the target cell (1). This process is mediated by the viral envelope glycoprotein complex gp120/gp41 (Env), 5 which interacts first with CD4 and then with a co-receptor, one of the chemokine receptors CCR5 or CXCR4 (2, 3).For the viral and cellular membranes to fuse, a critical number of gp120-CD4/coreceptor engagements are needed to establish an energetically productive fusion pore (4). HIV-1 can also be transmitted from infected to uninfected cells through cell to cell contacts, called virological synapses because of their similarities to the immunological synapse (5). As an example, CD4 and CXCR4 recruitment (6 -8) and local actin polymerization take place in both processes (6, 9 -11). Receptor clustering is regulated by two main factors: 1) insertion into specific membrane domains by lateral membrane receptor interactions (12) such as lipid rafts (13) or tetraspanin-enriched microdomains (14 -17); and 2) actin remodeling (6, 18 -20). This phenomenon is well illustrated by experiments in which HIV-1 contact induces CD4 and CXCR4 capping at the plasma membrane of target CD4 ϩ T lymphocytes (21,22). Receptor capping requires the formation of a subcortical...

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“…57 VS formation relies heavily on LFA-1-mediated adhesive interactions with ICAMs; thus LFA-1-mediated adhesion plays a critical role in cell-to-cell transmission. 58 To examine the effect of H52 on LFA-1-mediated adhesion in primary T cells, PHA-activated T cells were treated with increasing concentrations of H52 and PLM-2 and then added to soluble ICAM-1-coated plates. H52 inhibited cell adhesion to ICAM-1 in a dose-dependent fashion with inhibition observed at concentrations of 0.8 lg/ml and higher ( Fig.…”

Section: H52 Inhibits Lfa-1-mediated Cell-to-cell Adhesion In Primarymentioning

confidence: 99%

“…63 Virological synapses formed between HIV-1-infected T cells and uninfected target cells involves recruitment of HIV-1 receptors, coreceptors, adhesion molecules, and cytoskeletal proteins, and, like immunological synapses, relies on LFA-1-mediated adhesion to ICAM-1. 58,64 This in turn facilitates infection by directed budding and fusion of newly generated virions to interacting target cells. Interestingly, since adhesion molecules are recruited to virological synapses where virus budding also occurs, this may explain the efficient incorporation of adhesion molecules by HIV-1.…”

mentioning

confidence: 99%

Antibody Against Integrin Lymphocyte Function-Associated Antigen 1 Inhibits HIV Type 1 Infection in Primary Cells Through Caspase-8-Mediated Apoptosis

Walker

Cimakasky²,

Coleman

et al. 2013

AIDS Research and Human Retroviruses

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Adhesion Molecule Interactions Facilitate Human Immunodeficiency Virus Type 1-Induced Virological Synapse Formation between T Cells

Cited by 153 publications

References 35 publications

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

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

Actin-binding Protein Drebrin Regulates HIV-1-triggered Actin Polymerization and Viral Infection

Antibody Against Integrin Lymphocyte Function-Associated Antigen 1 Inhibits HIV Type 1 Infection in Primary Cells Through Caspase-8-Mediated Apoptosis

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