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Journal of Virology, October 2008, p. 9445-9457, Vol. 82, No. 19
0022-538X/08/$08.00+0 doi:10.1128/JVI.00835-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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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 Veteran Affairs New York Harbor Healthcare System, Manhattan Campus, and Department of Pathology, New York University School of Medicine, New York, New York 10010,2 Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India,3 Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 441064
Received 18 April 2008/ Accepted 9 July 2008
Human immunodeficiency virus type 1 (HIV-1)-infected T cells form a virological synapse with noninfected CD4+ T cells in order to efficiently transfer HIV-1 virions from cell to cell. The virological synapse is a specialized cellular junction that is similar in some respects to the immunological synapse involved in T-cell activation and effector functions mediated by the T-cell antigen receptor. The immunological synapse stops T-cell migration to allow a sustained interaction between T-cells and antigen-presenting cells. Here, we have asked whether HIV-1 envelope gp120 presented on a surface to mimic an HIV-1-infected cell also delivers a stop signal and if this is sufficient to induce a virological synapse. We demonstrate that HIV-1 gp120-presenting surfaces arrested the migration of primary activated CD4 T cells that occurs spontaneously in the presence of ICAM-1 and induced the formation of a virological synapse, which was characterized by segregated supramolecular structures with a central cluster of envelope surrounded by a ring of ICAM-1. The virological synapse was formed transiently, with the initiation of migration within 30 min. Thus, HIV-1 gp120-presenting surfaces induce a transient stop signal and supramolecular segregation in noninfected CD4+ T cells.
Published ahead of print on 16 July 2008.
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