It is known that Retroviruses, such as HIV, that are already within cells are much more easily transmitted when they spread through direct contact between cells than if they are floating free in the blood stream. However, how this contact stimulates virus- spreading has up until now been poorly understood. In this week's edition of the online open-access journal PLoS Biology, researchers at Yale University, led by Dr. Walther Mothes, have recorded movies of viral 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 Anti-Retroviral drugs.
"Cell-to-cell transmission is a thousand times more efficient, which is why diseases such as AIDS are so successful and so deadly," said Walther Mothes, associate professor of microbial pathogenesis at the Yale School of Medicine. "And because retroviruses spread through the tight cell-cell interface, they are out of reach for the immune system."
Using imaging technology that can track individual virus particles in real time, the 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 researchers report. 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 sticky viral protein called Env that docks with uninfected cells and then attracts the viral particles to these sites. If this adhesion molecule lacked a key element, a "cytoplasmic tail," then the viral particles did not assemble at the patches of contact 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 said. "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 anti-viral strategy based on targeting cell-to-cell transmission."
Source: Public Library of Science