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02756 INDUCTION AND INHIBITION OF THE HIV-1 VIROLOGICAL SYNAPSE IN T CELLS *Jolly Clare HIV-1 can spread either by release of cell-free virions or by direct cell-cell spread. Cell-cell spread has advantages for the virus such as production of new viral RNA and proteins that is more rapid than that observed after cell-free virus infection, and potential escape from elements of humoral immunity and inhibitors of viral entry. We have established a model system, based on conjugate formation between HIV-1-infected (effector) T cells and uninfected (target) T cells to analyse the molecular events taking place during cell-cell spread. Using this system we demonstrate that HIV-1 induces actin-dependent recruitment of the viral receptors, CD4 and CXCR4, and the adhesion molecue LFA-1, to the interface between effector and target cells. This has been termed a virological synapse. Formation of this synapse is followed by rapid transfer of viral Gag into the target cell, a process that probably takes place via directed fusion of virions with the target cell membrane. We have tested a number of inhibitors of this process and report that agents with potential for use as HIV-1 microbicides, including neutralising antibodies, anti-CD4 antibodies and small molecule inhibitors of the HIV-1-coreceptor interaction, are effective at preventing cell-cell transfer of HIV-1. These data are encouraging as they demonstrate that this mode of viral spread is susceptible to microbicidal intervention. Dr. Clare Jolly |
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