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!
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy