Cold sores, painful, unsightly blemishes around the mouth, have so far evaded a cure or even prevention. They're known to be caused by the herpes simplex virus 1 (HSV1), which lies dormant in the trigeminal nerve of the face until triggered to reawaken by excessive sunlight, fever, or other stresses.
"We have provided a molecular understanding of how HSV1 hides and then switches back and forth between the latent (hidden) and active phases," said Bryan Cullen, Duke professor of molecular genetics and microbiology.
His group's findings, published in Nature, also provide a framework for studying other latent viruses, such as the chicken pox virus, which can return later in life as a case of shingles, and herpes simplex 2 virus, a genitally transmitted virus that also causes painful sores, Cullen said.
Most of the time, HSV1 lives quietly for years, out of reach of any therapy we have against it. It does not replicate itself during this time and only produces one molecular product, called latency associated transcript RNA or LAT RNA.
"It has always been a mystery what this product, LAT RNA, does," Cullen said. "Usually viral RNAs exist to make proteins that are of use to the virus, but this LAT RNA is extremely unstable and does not make any proteins."
In studies of mice, the team showed that the LAT RNA is processed into smaller strands, called microRNAs, that block production of the proteins that make the virus turn on active replication. As long as the supply of microRNAs is sufficient, the virus stays dormant.
After a larger stress, however, the virus starts making more messenger RNA than the supply of microRNAs can block, and protein manufacturing begins again. This tips the balance, and the virus ultimately makes proteins that begin active viral replication.
The new supply of viruses then travels back down the trigeminal nerve, to the site of the initial infection at the mouth. A cold sore always erupts in the same place and is the source of viruses that might infect another person, either from direct contact, or sharing eating utensils or towels, Cullen said.
The approach to curing this nuisance would be a combination therapy, Cullen said. "Inactive virus is completely untouchable by any treatment we have. Unless you activate the virus, you can't kill it," he said.
Cullen and his team are testing a new drug designed to very precisely bind to the microRNAs that keep the virus dormant. If it works, the virus would become activated and start replicating.
Once the virus is active, a patient would then take acyclovir, a drug that effectively kills replicating HSV1.
"In principle, you could activate and then kill all of the virus in a patient," Cullen said. "This would completely cure a person, and you would never get another cold sore."
He and the team are working with drug development companies in animal trials to begin to answer questions about how to deliver this drug most effectively.
Mary Jane Gore | EurekAlert!
Something old, something new in the Ocean`s Blue
14.11.2019 | Max-Planck-Institut für Marine Mikrobiologie
AI-driven single blood cell classification: New method to support physicians in leukemia diagnostics
13.11.2019 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Dresden has succeeded in using Selective Electron Beam Melting (SEBM) to...
Carbon nanotubes (CNTs) are valuable for a wide variety of applications. Made of graphene sheets rolled into tubes 10,000 times smaller than a human hair, CNTs have an exceptional strength-to-mass ratio and excellent thermal and electrical properties. These features make them ideal for a range of applications, including supercapacitors, interconnects, adhesives, particle trapping and structural color.
New research reveals even more potential for CNTs: as a coating, they can both repel and hold water in place, a useful property for applications like printing,...
If you've ever tried to put several really strong, small cube magnets right next to each other on a magnetic board, you'll know that you just can't do it. What happens is that the magnets always arrange themselves in a column sticking out vertically from the magnetic board. Moreover, it's almost impossible to join several rows of these magnets together to form a flat surface. That's because magnets are dipolar. Equal poles repel each other, with the north pole of one magnet always attaching itself to the south pole of another and vice versa. This explains why they form a column with all the magnets aligned the same way.
Now, scientists at ETH Zurich have managed to create magnetic building blocks in the shape of cubes that - for the first time ever - can be joined together to...
Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...
In two experiments performed at the free-electron laser FLASH in Hamburg a cooperation led by physicists from the Heidelberg Max Planck Institute for Nuclear physics (MPIK) demonstrated strongly-driven nonlinear interaction of ultrashort extreme-ultraviolet (XUV) laser pulses with atoms and ions. The powerful excitation of an electron pair in helium was found to compete with the ultrafast decay, which temporarily may even lead to population inversion. Resonant transitions in doubly charged neon ions were shifted in energy, and observed by XUV-XUV pump-probe transient absorption spectroscopy.
An international team led by physicists from the MPIK reports on new results for efficient two-electron excitations in helium driven by strong and ultrashort...
05.11.2019 | Event News
30.10.2019 | Event News
02.10.2019 | Event News
14.11.2019 | Materials Sciences
14.11.2019 | Physics and Astronomy
14.11.2019 | Information Technology