New target identified to prevent cold sores and genital herpes

New target identified to prevent cold sores and genital herpes

Scientists have a new goal to prevent cold sores after researchers at the University of Virginia School of Medicine discovered an unexpected way the herpes virus reactivates in the body. The finding could also have important implications for genital herpes, which are caused by the same virus.

The discovery by UVA's Anna Cliffe, PhD, and colleagues seems to defy common sense. She and her team determined that the silting herpes virus will make a protein to trigger the body's immune response as part of its escape from rest. You would think that this would be bad for the virus - that activating the body's antiviral defenses would be like petting a bear. But instead, it's the opposite: The virus ramps up the antiviral process in infected neurons (nerve cells) to make the kind of comeback no one wants.

Our results identify the first viral protein that is required for the herpes simplex virus to awaken from dormancy, and surprisingly, this protein does so by triggering responses that should work against the virus. This is important because it gives us new ways to potentially prevent the virus from waking up and activating immune responses in the nervous system that could have long-term negative consequences. “

Anna Cliffe, PhD, UVA Department of Microbiology, Immunology and Cancer Biology

Understanding herpes simplex virus-associated disease

Cold sores are primarily caused by herpes simplex virus 1 (HSV-1), one of two forms of the herpes virus. HSV-1 is highly contagious, and more than 60% of people under the age of 50 have been infected worldwide, the World Health Organization estimates. That's more than 3.8 billion people.

In addition to fever sores, herpes simplex virus 1 can also cause genital herpes. Remarkably, the UVA researchers found that herpes simplex virus 2 also makes the same protein and can use a similar mechanism to be reactivated. So the new discovery of UVA may also lead to new treatments for genital herpes.

In addition to cold sores and herpes, HSV-1 can also cause viral encephalitis (brain infection) and has been linked to the development of Alzheimer's disease.

Once HSV-1 enters our body, it stays forever. Our immune systems can trick it into hiding, so infected people can be symptom-free. But stress, other infections and even sunburns are known to cause flare-ups. UVA's new discovery adds another surprising way it may spring back into action.

The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection. Scientists believe this is because the infections trigger certain “sensing pathways” that act as a home security system for neurons. Detection of a pathogen alone may be enough to trigger the herpes virus to replicate, the scientists believe, even in cases of "abortive infections" - when the immune system contains the new pathogen before it can repeat itself.

“We were surprised that HSV-1 does not just passively wait for the right conditions to actively reactivate the threat and take control of the process,” said researcher Patryk Krakowiak. "Our results suggest that the virus can use immune signals to use cellular stress - whether from neuron damage, infection or other threats - as a cue to escape its host and find a new one."

With new understanding of how herpes flares can be triggered, scientists may be able to target the protein to prevent them, researchers say.

“We are now pursuing this work to study how the virus ramps up this response and testing inhibitors of UL12.5 function,” Cliffe said. "Currently, there are no therapies that can prevent the virus from waking up from dormancy, and this stage has been thought to utilize only host proteins. Developing therapies that specifically target a viral protein is an attractive approach that is likely to have fewer side effects than targeting a host protein."

Results published

The researchers published their results inPNAsTheProceedings of the National Academy of Sciences. The research team consisted of Patryk A. Krakowiak, Sean R. Cuddy, Matthew E. Flores, Abigail L. Whitford, Sara A. Dochnal, Aleksandra Babnis, Tsuyoshi Miyake, Marco Tigano, Daniel A. Engel, and Cliffe. The scientists have no financial interest in the work.

The research was supported by National Institutes of Health grants R21AI171544, T32AI007046, T32GM008136, and R01AG085782, as well as the Owens Family Foundation, a UVA Global Infectious Disease Institute Institute, and UVAWAGNER grants.

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