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 Penn’s 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” it long enough to take a snapshot.
Knowing that virus-cell fusion starts when gD binds to a cell receptor, these researchers monitored the remaining protein interactions using bimolecular complementation, a newly developed process that employs, in this case, a protein called Venus. Venus, like the planet, shines brightly against a dark background. Researchers split the yellow Venus protein in two, creating tags which were stitched to either gB or gH, the proteins they believed played a role in fusion. When Venus is split in half, it no longer glows yellow. But when half-Venus-gB and half-Venus-gH combine, even very briefly as they do, the two halves of Venus interact and shine again.
The team used microscopy to look for the viral protein-protein interactions during fusion and thus found that fusion requires proteins gB, gH and gL, called the “core fusion machinery” of all herpes viruses.
“This is a complex mechanism we’re looking at,” Gary Cohen, professor of microbiology in Penn’s School of Dental Medicine, said. “We still have a long way to go but this is a major step forward for us and the field, and now we have a new toy to play with to help us with a whole new set of questions. That is the fun of science: there is always another question. “
Jordan Reese | EurekAlert!
A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich
New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
17.02.2017 | Medical Engineering
17.02.2017 | Medical Engineering
17.02.2017 | Health and Medicine