Herpes: Researchers inhibit "on" switch
Inhibitor could prevent herpes symptoms before they occurRead out
Tricked herpes: researchers have discovered the key switch that can be active in herpes virus stress. It allows the viruses to multiply in the nerve cells despite blockage of their genome and then to attack the skin and other tissues. The trick: this switch can be blocked by an inhibitor, as researchers demonstrated on mouse neurons. If this succeeds also in humans, this could prevent herpes symptoms before they arise.
Who has herpes knows the phenomenon: The annoying bubbles always bloom when you are in stress or carries an infection in itself. The reason: Once infected, the herpes simplex virus remain in the body for life and nests in the fine nerve endings of the skin and the continuing nerve fibers. A few years ago, researchers discovered that certain immune cells, the T-memory cells, play an important role in keeping the viruses there under control.
But what exactly happens when stress activates the herpes virus remained unclear. Because in this state are inserted into Zellerbgut genes of the virus partially blocked for reading. It is hardly possible to produce new viruses. There must therefore be a switch that releases the virus and sets the virus propagation in motion. But where?
Stress hormone activates herpes viruses
Anna Cliffe of the University of North Carolina and her colleagues have now explored this in mice. They considered that mouse neurons in culture that were infected with herpes simplex. Initially, the viruses were in their latent phase: they were inactive, did not multiply and did not emerge from their "hiding place" in the nerve. Next, the researchers put the infected nerve fiber under stress by adding stress hormones.Green fluorescence labeled herpes viruses become active in a culture of nerve fibers. © Anna Cliffe / UNC
It turned out: This stress actually triggered a virus multiplication, the herpes virus soon began to emerge in droves from the neurons. In humans, this would cause a cold sore or even a more severe herpes episode, as the researchers explain. Immediately before the virus came out, however, something else happened in the nerve fiber: a certain sequence of proteins was activated. display
Switch on the virus genetic material
Even more exciting, however: this JNK protein cascade turned out to be the crucial helper of the herpes virus. Because once these proteins are present, they allow the virus to push aside the normally blocking methyl linkages from its genome. This is done with the help of accumulating phosphorus groups.
"Normally, the methyl groups prevent the reading of genes, " says senior author Mohanish Deshmukh of the University of North Carolina. "But this phosphorylation releases the brakes just enough to read and copy some of the viral genetic material." Stress activates this methyl / phospho switch, which in turn helps the herpes virus multiply.Herpes simplex viruses under the electron microscope CDC
Chance for more effective therapy against herpes
The identification of this switch could even be very useful. Because as the experiments also showed, he lets himself be blocked. When the researchers put the JNK protein cascade in their mouse neurons by an inhibitor out of force, the virus multiplication remained. "That had a spectacular effect, " says Deshmukh. "If we blocked JNK, the virus could not reactivate."
According to the researchers, this inhibition could also work in humans and thus offer a new and better chance of controlling the herpes. "The proteins that are needed for viral reactivation are only found in nerve cells they are therefore a good, specific starting point for therapies, " says Cliffe. Therefore, this mechanism has to be proven next to human neurons.
However, if this succeeds, then new drugs for the herpes virus and its relatives could be developed on this basis. Because they prevent the proliferation of the virus even before the first symptoms, the time of the angry lip blisters could be over. (Cell Host & Microbe, 2015; doi: 10.1016 / j.chom.2015.11.007)
(University of North Carolina Health Care, Dec 10, 2015 - NPO)