Cell-to-cell transmission of retroviruses
Retroviruses, such as HIV, that are already within cells are more easily transmitted when they spread through direct contact between cells than if they are floating free in the bloodstream. Researchers have recorded video of virus activity within cells that helps explains why cell-to-cell transmission is so efficient and may in turn provide insights into potential targets for a new generation of antiretroviral drugs.
Cell-to-cell transmission of retroviruses is a thousand times more efficient than extracellular infection, and because retroviruses spread through the tight cell-cell interface, they are out of reach of the immune system. Using imaging technology that can track individual virus particles in real time, the research team discovered that retrovirus-infected cells can specifically assemble daughter viruses at the point of contact between cells. Ten times more of these particles are found at these cellular connection points than elsewhere at the surface of cells. The ability of infected cells to specifically produce viruses only at cell interfaces offers an explanation of how viruses spread so efficiently. The team identified a clue to how virus assembly is targeted to these points of contact: it involves a retrovirus protein called Env that docks with uninfected cells and then attracts the viral particles to these sites. If this adhesion molecule lacked a cytoplasmic tail, then the virus particles did not assemble at the patches of contact between cells.
Somewhere down the road it is possible that we may be able to develop completely new antiviral strategies based on targeting cell-to-cell transmission.
Assembly of the Murine Leukemia Virus Is Directed towards Sites of Cell–Cell Contact. 2009 PLoS Biol 7(7): e1000163 doi:10.1371/journal.pbio.1000163
We have investigated the underlying mechanism by which direct cell–cell contact enhances the efficiency of cell-to-cell transmission of retroviruses. Applying 4D imaging to a model retrovirus, the murine leukemia virus, we directly monitor and quantify sequential assembly, release, and transmission events for individual viral particles as they happen in living cells. We demonstrate that de novo assembly is highly polarized towards zones of cell–cell contact. Viruses assembled approximately 10-fold more frequently at zones of cell contact with no change in assembly kinetics. Gag proteins were drawn to adhesive zones formed by viral Env glycoprotein and its cognate receptor to promote virus assembly at cell–cell contact. This process was dependent on the cytoplasmic tail of viral Env. Env lacking the cytoplasmic tail while still allowing for contact formation, failed to direct virus assembly towards contact sites. Our data describe a novel role for the viral Env glycoprotein in establishing cell–cell adhesion and polarization of assembly prior to becoming a fusion protein to allow virus entry into cells.
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Tags: Biology, HIV/AIDS, infection, Microbiology, Microscopy, Science, Video, Virology, virus
