PHILADELPHIA - University of Pennsylvania researchers have uncovered an important step in how herpes simplex virus, HSV-1, uses cooperating proteins found on its outer coat to gain entry into healthy cells and infect them. Further, the studys authors say, they have demonstrated the effectiveness of monitoring these protein interactions using biomolecular complementation.
The findings, published in the Proceedings of the National Academy of Sciences, provide a better understanding of the mechanism that viruses use to conquer healthy cells.
Beginning with the knowledge that HSV-1 glycoprotein gD binds to cell receptors in a healthy cell to begin virus-cell fusion, researchers questioned how other proteins combined or cooperated on the attack. They tagged additional HSV-1 proteins with a fluorescent marker to witness the complex battle, thus demonstrating that gD somehow signals to three other herpes proteins -- gB, gH and gL -- to swing into action, continuing fusion and ultimately releasing the viral genome into the cell. Once in the cell, the viral genome takes over and directs the cell to make more virus.
Watching these proteins interact tells us a lot about HSV and other herpes viruses and how they attack the body, Roselyn Eisenberg, professor of microbiology in Penns School of Veterinary Medicine, said. The first thing this virus does when it finds a cell is fool the cell into thinking the virus is a welcome guest when it is actually a dangerous intruder. But getting in is not easy. It takes four viral proteins to do it, and they must cooperate with each other in ways that we are only beginning to understand.
Monitoring the interactions required a novel technique. Researchers assumed in their hypothesis that these proteins had to physically interact with each other but could not demonstrate the split-second interaction. Penn researchers hypothesized that the encounter might be too brief and decided to look for ways to freeze
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| Contact: Jordan Reese jreese@upenn.edu 215-573-6604 University of Pennsylvania Source:Eurekalert |