4.6 Article

Human immunodeficiency virus type 1 envelope gp120 induces a stop signal and virological synapse formation in noninfected CD4+ T cells

Journal

JOURNAL OF VIROLOGY
Volume 82, Issue 19, Pages 9445-9457

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00835-08

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Categories

Funding

  1. NIH [AI43542, AI44931, AI-060503, AI071815]
  2. U. S. Department of Veterans Affairs
  3. New York University Center for AIDS Research [AI-27742]
  4. Case Western Reserve University Center [AI-36219]
  5. Training Program in TB
  6. HIV Prevention and Treatment [D43 TWO1409]

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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.

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