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Journal of Virology, November 2009, p. 11341-11355, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01440-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Envelope gp120-Induced Partial T-Cell Receptor Signaling Creates an F-Actin-Depleted Zone in the Virological Synapse {triangledown} ,{dagger}

Gaia Vasiliver-Shamis,1 Michael W. Cho,2 Catarina E. Hioe,3 and Michael L. Dustin1*

Program in Molecular Pathogenesis, Marty and Helen Kimmel Center for Biology and Medicine, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York 10016,1 Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106,2 Veterans Affairs New York Harbor Healthcare System, Manhattan Campus, and Department of Pathology, New York University School of Medicine, New York, New York 100103

Received 13 July 2009/ Accepted 25 August 2009

Cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1) occurs via a virological synapse (VS), a tight cell-cell junction formed between HIV-infected cells and target cells in which the HIV-1-infected cell polarizes and releases virions toward the noninfected target cell in a gp120- and intercellular adhesion molecule 1 (ICAM-1)-dependent process. The response of the target cell has been less studied. We utilized supported planar bilayers presenting gp120 and ICAM-1 as a reductionist model for the infected-cell membrane and investigated its effect on the target CD4 T cell. This study shows that HIV-1 gp120 interaction with its receptors is initially organized into microclusters that undergo F-actin-dependent consolidation into a central supramolecular activation complex (cSMAC). Src kinases are active in both gp120 microclusters and in the VS cSMAC. The early T-cell receptor (TCR) signaling machinery is partially activated at the VS, and signaling does not propagate to trigger Ca2+ elevation or increase CD69 expression. However, these partial TCR signals act locally to create an F-actin-depleted zone. We propose a model in which the F-actin-depleted zone formed within the target CD4 T cell enhances the reception of virions by releasing the physical barrier for HIV-1 entry and facilitating postentry events.

* Corresponding author. Mailing address: Department of Pathology, Program in Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016. Phone: (212) 263-3207. Fax: (212) 263-5711. E-mail: michael.dustin{at}med.nyu.edu

{triangledown} Published ahead of print on 26 August 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, November 2009, p. 11341-11355, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01440-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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