Cell-to-cell Transmission of Retroviruses
The spread of retroviruses among cells is estimated to be 2-3 orders of magnitude more efficient when cells can physically interact with each other. The underlying mechanism is largely unknown, but transfer is believed to occur through large-surface interfaces, called virological or infectious synapses. To understand retroviral spreading, we co-culture infected cells generating fluorescent murine leukemia viruses (MLV) with receptor expressing target cells and monitor viral spreading by time-lapse microscopy. This resulted in the first documentation of cell-to-cell transmission of retroviruses in living cells. Viruses were observed to walk from cell to cell via thin filopodial bridges (see Movie below). While we are currently using this model system to understand the mechanism of cell-to-cell transmission of MLV, we have also turned our attention to HIV. The AIDS epidemic is driven by the ability of HIV to efficiently spread from cell to cell. Our focus in this area is directed towards the isolation of new host factors required for the spreading of HIV as well as the identification of small molecule inhibitors that can interfere with this step.
Murine leukemia virus (green/red) is seen walking along thin filopodial bridges from the infected cell, seen to the left, towards the target cells to the right. This mechanism of transmission involves the initial generation of a filopodial bridge between the infected cell and the target cell. The viral Env glycoprotein expressed in infected cells functions as an adhesion protein to stably anchor target cell filopodia in infected cells thereby generating a stable bridge. Viruses then move along the outer surface of the filopodial bridge toward the target cell.