Scientists discovered a new path to prevent fever bubbles

Scientists have uncovered a surprising strategy that used the herpes simplex virus (HSV-1) to wash again in the body. A new study by the Medical School of Medicine at the University of Virginia has identified a viral protein, UL12.5, that plays a key role in triggering viral reactivation.

The discovery questions the conventional understanding of how the virus of the rest break escapes and could lead to new treatments for fever bubbles and herpes in the genital.

HSV-1 is a very contagious virus that, according to the World Health Organization, infects over 60% of people under 50 worldwide. As soon as the virus in the body is in the body, it places a lifelong presence that rests in nerve cells until they are reactivated by stress, illness or even sunlight.

While HSV-1 is typically connected to fever bubbles, it can also cause herpes in genital and encephalitis and connected to neurodegenerative diseases such as Alzheimer's.

When HSV-1 infects a cell, the immune system recognizes its presence by pattern recognition receptors (PRRS) that capture viral components. These receptors activate paths to eliminate the infection. However, viruses have developed mechanisms to avoid or manipulate these immune system.

A particularly surprising discovery is that HSV-1 is not only waiting for favorable conditions to become reactivated-it is actively participating in its own re-wash by triggering an immune response.

Researchers of UVA under the direction of Anna Cliffe, Ph.D.

Ul12.5 aims at mitochondria, the energy -producing structures of the cell, which releases them mitochondrial DNA (MTDNA) into the cytosol. This triggers the CGAS-Sting path, an important mechanism for immune response that typically combats infections.

Under normal circumstances, CGAS recognizes foreign DNA in cytosol and activates Sting, which initiates the production of interferons and other antiviral molecules.

However, HSV-1 uses this path to reappear from the rest delivery. By inducing mitochondrial stress and the release of MTDNA, UL12.5 places a chain reaction that promotes viral gene expression and reactivation.

“We were surprised to find that HSV-1 is not only passive for the right conditions to actively recognize the risk and to take control of the process,” said researcher Patryk Krakowiak. “Our results suggest that the virus uses immunosignals to recognize cellular stress – whether by neuronal damage, infections or other threats – as an indication of the host and find a new one.”

Understand how HSV-1 manipulated the immune system opens the door to new therapeutic strategies. Current antiviral medicines such as Acyclovir only suppress viral replication during active infection, but cannot prevent reactivation. The discovery of the role of Ul12.5 When awakening the virus indicates that the targeting could prevent this protein outbreaks.

“We are now pursuing this work to investigate how the virus kidnaps this reaction and test inhibitors to the UL12.5 function,” said Cliffe. “At the moment there are no therapies that can prevent the virus from waking out of the rest packages, and it was assumed that this level only use host proteins. The development of therapies that act specifically on a viral protein is an attractive approach that will probably have fewer side effects than the targeting of an inn. “

The study also showed that in cases in which another infection was available, HSV-1 did not need UL12.5 for reactivation. Instead, the immune response triggered by the second infection was sufficient to wake up the virus. This indicates that HSV-1 can use several ways to further reactivate the treatment strategies and continue to complicate it.

HSV-1 was associated with serious neurological diseases via farm wounds and herpes in the genital. Some studies suggest that chronic inflammation from repeated HSV-1 reactivation can contribute to diseases such as Alzheimer's. The ability of HSV-1 to manipulate immune paths in neurons raises concerns about the long-term effects on the health of the brain.

The virus establishes the latency in neurons, where it remains to rest until certain diseases trigger reactivation. The lack of viral proteins during the latency means that HSV-1 is based on the signal paths of the host to initiate reactivation. Such a path includes interleukin-1β (IL-1β), an inflammatory cytokine. Earlier studies have shown that IL-1 & BGR; HSV-1 reactivation can induce the increase in neuronal excitability.

“Our results identify the first viral protein that is necessary for the Herpes simplex virus to wake up from the break, and surprisingly, this protein does this by triggering answers that should work against the virus,” said Cliffe. “This is important because we may have new opportunities to prevent the virus from awakening and activity in the nervous system that could have negative consequences in the long term.”

With these new findings, scientists hope to develop treatments that prevent HSV 1 reactivation in their earliest stage. The inhibition of UL12.5 or the blocking of the mitochondrial DNA release could be a strategy to reduce outbreaks and to prevent the long-term inflammatory effects associated with recurring infections.