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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 Ca(2+) 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.

Original publication




Journal article


J Virol

Publication Date





11341 - 11355


Actins, Adaptor Proteins, Signal Transducing, CD3 Complex, CD4-Positive T-Lymphocytes, Cell Membrane, Cells, Cultured, Enzyme Activation, HIV Envelope Protein gp120, HIV-1, Humans, Intercellular Adhesion Molecule-1, Intercellular Junctions, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Membrane Proteins, Phospholipase C gamma, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-fyn, Receptors, Antigen, T-Cell, Signal Transduction, Virus Internalization, ZAP-70 Protein-Tyrosine Kinase