Like hobos on a train, HIV uses a preexisting transport system to leave one infected cell and infect new ones, according Johns Hopkins Medicine scientists have discovered. Their findings, published in the June issue of PLoS Biology, counter the prevailing belief that HIV and other retroviruses can leave and enter cells by virus-specific mechanisms only.
'Cells make HIV and other retroviruses by a naturally occurring export mechanism,' says Stephen Gould, professor of biological chemistry at Johns Hopkins. Cells normally export certain membrane-bound molecules by means of small sacs known as exosomes. 'Surprisingly, all that's needed for a protein to get out of the cell in exosomes are the ability to clump together and attach to the cell's membrane.'
In one experiment Gould and his team added chemicals to normal human cells that force nearby proteins together into a clump; this was enough to get them sent out of the cell in exosomes. If they added a tether to force naturally clumping proteins inside the cell to the membrane, the proteins met a similar exosomal deportation fate.
Gag, a major HIV protein, has both of these properties that cells sense in selecting exosomal cargoes. When the researchers removed the tethers or clumping signals from Gag, it could no longer get out of the cell to eventually infect others. However, if they were replaced with synthetic membrane anchors and clumping domains, Gag regained its ability to get out of cells in exosomes.
Gould speculates that cells may have initially developed exosomes as a quality control mechanism to get rid of clumped proteins, which are generally broken and useless. However, just as retroviruses exploit other cell processes for their own ends, it appears that they rely on exosomes to get out of infected cells and infect fresh cells. Because of this, researchers say, medications that interfere with exosome formation could be one way to inhibit HIV infections.