Researchers at the University of Pennsylvania School of Medicine have discovered part of the reason why cold sores, caused by a herpes virus, come back again and again. The new study, published online last month in Nature, points to a small RNA molecule, called a microRNA (miRNA) as the culprit that keeps the latent virus-infected cell alive. These findings could one day lead to a new way to fight the virus and offers the first target for intervention in the latent infection.
A research team led by Nigel W. Fraser, PhD, Professor of Microbiology, has found that herpes simplex virus-1 (HSV-1), the virus that causes cold sores and ocular keratitis, produces an miRNA molecule. This miRNA is encoded by the Latency-Associated Transcript gene (LAT) in the viral genome and works through a process called RNA interference to prevent normal cell death or apoptosis. Thus, the latent viral infection is maintained for the lifetime of the individual because the latently infected cell does not die.
"Although miRNAs encoded by cellular genes are known to be an important mechanism for controlling gene expression, this is one of the first miRNA found to be encoded by a viral genome," says Fraser. "Our study helps show how HSV-1 can maintain a latent infection for the lifetime of an infected individual."
The LAT gene was discovered by Fraser and colleagues in 1984, but a protein product from this gene has never been found. This caused Fraser and his research team to hypothesize that LAT may work through an miRNA molecule, which is a small piece of the LAT gene. It interferes with the translation of two cell proteins that are required for cell death: TGF-b and SMAD-3. The LAT miRNA binds to specific sequences of messenger RNA from these two genes and causes them to be degraded. Thus, the amount of TGF-b and SMAD-3 protein is reduced in the cell and apoptosis is prevented. Because the latent virus is not producing any viral proteins the immune system of the infected individual cannot detect the infected cell.
Latent HSV-1 infections form in neuronal cells of the peripheral nervous system. When a latent infection is reactivated (by stress of many kinds), HSV-1 proteins are synthesized and new infectious virus particles are formed. These virus particles migrate along the neuronal axons to the epithelial cells of the skin. Viral growth in the skin, or other mucous membranes where nerves are found, causes cell damage and an immune reaction that results in a painful sore. Although the latency-to-reactivation process is not fully understood, it is known to involve stress, such as physical damage, ultraviolet light, hormones, or even fever.
Fraser is currently testing whether HSV-2, a relative of HSV-1 that causes genital herpes, also encodes an miRNA molecule in its LAT gene. "MiRNA may be a more general mechanism that latent viruses use to remain alive in the host cell," suggests Fraser.
Present treatments of HSV-1 rely on acyclovir-based drugs that target the viral polymerase and inhibit viral DNA replication during the acute infection. However, they do not target the latent infection, and thus cold sores return throughout the lifetime of the infected individual. Finding an miRNA that interacts with the cellular TGF-b pathway during latency offers the first target against the latent infection and offers a profoundly different approach to treatment, concludes Fraser.
Karen Kreeger | EurekAlert!
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
If solubilty is the problem - Mechanochemistry is the solution
25.05.2018 | Technische Universität Dresden
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
25.05.2018 | Life Sciences
25.05.2018 | Interdisciplinary Research
24.05.2018 | Ecology, The Environment and Conservation