Misery loves company— just ask a retrovirus

YALE (US)—Retroviruses like HIV that are already inside cells are more easily transmitted when they are close to uninfected cells than if they are floating free in the bloodstream. The findings help explain how viruses spread efficiently.

“Cell-to-cell transmission is a thousand times more efficient, which is why diseases such as AIDS are so successful and so deadly,” explains Walther Mothes, associate professor of microbial pathogenesis at the Yale University School of Medicine. “And because the retroviruses are already in cells, they are out of reach of the immune system.”

Mothes and Jing Jin, a postdoctoral associate in Mothes’ lab, have made movies of viral activity within cells that reveal that infected cells can specifically produce viruses at the point of contact. Ten times more of these particles are found at these cellular poles than elsewhere at the surface of cells.

The ability of infected cells to specifically produce viruses only at cell-cell interfaces explains how viruses spread so efficiently, the researchers say.

The researchers also identified a possible weakness in the transmission chain. The team found that viruses express a sticky protein that docks with uninfected cells and then attracts viral assembly to these sites. If this adhesion molecule lacked a “cytoplasmic tail,” then the viral particles did not assemble at the jumping off point between cells.

Mothes expects many more such targets will be identified as scientists work out the mechanics of cell-to-cell transmission.

“We are just opening the door to this whole process,” Mothes says. “It is a black box, and many, many cellular factors have to be involved in making this happen. Our hope is that somewhere down the road we will have a completely new antiviral strategy based on targeting cell-to-cell transmission.”

The work was funded by the National Cancer Institute and amfAR, the Foundation for AIDS Research. The team’s findings appear in the July 27 edition of the open access journal PLoS Biology.

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