The discovery of soreness can pave the way for preventive treatment of oral, genital herpes

In findings challenging routine understandings of viral behavior, researchers at the University of Virginia have identified how the herpes virus sly manipulates our own immune defenses to trigger those unwelcome ice patterns.

The discovery, published in the Proceedings of the National Academy of Sciences, reveals that herpes simplex virus 1 (HSV-1) deploys a surprising strategy when reactivated from dormancy, intentionally igniting the body’s immune response as part of its escape plan.

“Our findings identified the first viral protein needed by herpes simplex virus to wake up from dormancy, and surprisingly, this protein does this by triggering responses to the action of the virus.

This counterintuitive approach (the virus intentionally reminds the immune system) represents a major shift in how scientists understand herpes reactivation. Instead of hiding to avoid detection, the virus deliberately triggered a wake-up call.

Six senses of the virus

The team found that HSV-1 produced a protein called UL12.5 to rejuvenate itself from dormancy. Although we have long known that stress, sunburns and other infections can trigger cold sores, this protein provides a previously unknown internal mechanism of viral reactivate.

“We were surprised to find that HSV-1 not only passively waits for the right conditions to reactivate, but also actively feels the danger and controls the process,” explains researcher Patryk Krakowiak. “Our findings suggest that the virus may use immune signals to detect cellular stress (whether it is neuronal damage, infection or other threats) as a prompt to escape its host and find a new host.”

According to the World Health Organization estimates, this discovery has a significant impact, with approximately 3.8 billion people considering HSV-1 infected more than 60% of people under the age of 50 worldwide.

Beyond cold arses

Although many people mainly associate HSV-1 with those annoying lipsticks, its effects further expand. The virus can cause genital herpes (now, more new cases attributed to HSV-1 than HSV-2), viral encephalitis (brain inflammation), and is associated with the development of Alzheimer’s disease.

Researchers in Virginia also found that Herpes Simplex 2, which traditionally causes most cases of genital herpes, produces the same protein and may use similar reactivation mechanisms. This suggests that this finding may lead to the treatment of oral and genital herpes.

Perhaps most fascinating is that the team’s observation is that the UL12.5 protein does not require viral reactivate when another infection occurs. Scientists believe this is because other infections trigger certain “sensing pathways” (actually neuronal equivalents of home security systems), so the herpes virus can be detected and developed.

A persistent problem

Once HSV-1 infects someone, it stays in their body forever. The immune system can force it to hibernate, thus keeping people asymptomatic for a long time. However, the new study shows that the virus not only waits passively during dormant, but also actively monitors its environment for opportunities to reappear.

The virus appears to be able to hijack the same immune response designed to protect us, turning our defenses into signals of its reactivate. This helps explain why many different triggers from emotional stress to sunburn can cause cold sores in different individuals.

Towards better treatment

While current antiviral drugs can help manage outbreaks, there are no existing therapies that can prevent the virus from reactivateing in the first place. UVA discovery may change this prospect.

“At present, there is no therapy that prevents the virus from hibernation, and this stage is considered to use only host proteins,” Cliff noted. “Developing a therapies specifically targeting viral proteins is an attractive approach, which may be less than targeting host proteins.”

The research team is already pursuing this promising avenue.

“We are now focusing on this work to investigate how the virus hijacks this response and tests inhibitors of ul12.5 function,” Cliffe said.

This study represents a meaningful step towards preventive treatment that can prevent sores before they begin. For billions of people around the world who have experienced the discomfort and social embarrassment of herpes outbreaks, this development will be a welcome relief, and it is a surprisingly crafty way to understand that this ancient virus has evolved to bring our defense beyond ours.

The study was funded by various grants from the National Institutes of Health, the Owens Family Foundation, the UVA Global Infectious Diseases Institute Seed Award, and the UVA Wagner Scholarship.