The cytoplasmic talk of retroviruses helps them spread from cell to cell
Press release from PLoS Biology
27-Jul-2009 - 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."
Funding:The work is supported by a grant from the National Cancer Institute ROI CA098727 to WM and a fellowship from amfAR Foundation for AIDS research to JJ. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests statement: The authors declare that no competing interests exist.
Citation: Jin J, Sherer NM, Heidecker G, Derse D, Mothes W (2009) Assembly of the Murine Leukemia Virus Is Directed towards Sites of Cell-Cell Contact. PLoS Biol 7(7): e1000163. doi:10.1371/journal.pbio.1000163
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000163
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