104 Cell-to-cell transmission of HIV: role of virological synapse

HIV-1 infects CD4+ T-lymphocyte by cell free viral particles released from the surface of effector cells or after the formation of intercellular contact between infected cell and healthy lymphocyte. The last way of infection was designated as cell-to-cell viral transmission. The current studies suggest that cell-to-cell transmission of HIV occurs in peripheral lymph nodes at the early stage of infection and is more efficient pathway of virus dissemination than cell-free infection. One of the most accepted models of HIV transmission is the formation of virological synapse (VS); tight intercellular adhesion junction sharing structural similarity with immunological synapse. VS forms after HIV surface protein gp120 expressed on the plasma membrane of infected cells in prefusogenic conformation recognizes CD4 receptor on target cell. Viruses transmitted across VS undergo endocytosis by target cells, so that viral entry occurs via endocytic compartments and not via cell surface. This feature of cell-to-cell transmission accounts for the resistance of HIV to the neutralizing antibodies. Although the different stages of HIV cell-to-cell transmission have been extensively studied, the levels of correlation between virus transmission and targets infection were not accurately quantified. To fill up the gap in our understanding of cell-mediated viral infection, we have developed a new methods and improved vectors to quantify the levels of VS formation, cell-to-cell infection, and macromolecular transport across the cell-cell contact. New T cell lines stably producing recombinant virus like particles and reporter RNA, as well as modified target cells were generated.