119 HIV-1 envelope gp120 induces a stop signal and virological synapse formation in non-infected CD4+ T cells

Abstract

HIV-1-infected T cells form a virological synapse (VS) with non-infected 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 sustained interaction between T cell and antigen-presenting cells. In this study we have asked whether HIV-1 envelope gp120 presented on a surface to mimic an HIV-1 infected T cell also delivers a stop signal and if this is sufficient to induce a virological synapse. Using transmigration assay 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. The VS dynamics were evaluated using real-time fluorescence imaging of non-infected CD4+ T cells on a glass-supported planar bilayer containing HIV-1 gp120 and ICAM-1. The data reveal for the first time high-resolution en-face images of VS that is characterized by segregated supramolecular structures with a central cluster of HIV-1 gp120 surrounded by a ring of ICAM-1. Interestingly, unlike the immunological synapse that can be stable for >1 hour, the VS was formed transiently with initiation of T cell migration within 30 minutes. Both the stop signal and VS formation required HIV-1 gp120 interaction with CD4 but not the chemokine receptor. Thus, HIV-1 gp120-presenting surfaces induce a transient stop signal and supramolecular segregation in non-infected CD4+ T cells by a CD4-dependent manner. The HIV-1 gp120-induced transient arrest and VS assembly may constitute an efficient mechanism for virus transfer from infected cells to target cells without incurring cell-cell fusion that terminates the virus life cycle.