Human cytomegalovirus (CMV) belongs to the herpesvirus family and is of clinical importance, especially during pregnancy or in immunosuppressed patients such as transplant recipients. Research teams led by the virologists Thomas Gramberg (University Hospital Erlangen) and Michael Schindler (University Hospital Tübingen) report in the latest issue of the renowned journal Nature Microbiology how CMV ensures the supply of essential DNA building blocks for the replication of the viral genome, the so-called nucleotides.
In detail, the virus blocks the cellular enzyme SAMHD1, which regulates the provision of nucleotides through its activity. Normally, this protects the cell from infectious pathogens and ensures proper genome replication and repair, which also prevents the development of tumors. Thus, the knowledge gained in these studies is an important basis for novel therapies against DNA viruses and cancer.
The researchers were able to show that both human and murine CMV code for a protein, namely the viral kinase pUL97 or M97, which modifies SAMHD1 and thus inactivates it.
"In infected mice that were genetically manipulated in such a way that they did not express SAMHD1, we found a strongly increased CMV replication," explains Janina Deutschmann, PhD student in the laboratory of Prof. Gramberg and first author of the mouse study.
"The effect was even more pronounced when the viruses no longer encoded the kinase M97 to inactivate SAMHD1," she continues. Dr. Ramona Businger, first author of the second study in Prof. Schindler's laboratory, also investigated the effects in the human system. "A drastic increase in SAMHD1 phosphorylation was observed in primary human immune cells after CMV infection. We were able to directly relate this to the activity of the viral kinase pUL97," explains Dr. Businger.
However, there are also differences between humans and mice. While murine CMV seems to switch off SAMHD1 only by its kinase, its human counterpart also targets the production of SAMHD1. This shows how important this factor is for virus replication.
It is also known that other viruses, and probably also tumor cells, have to inactivate SAMHD1 as well in order to multiply efficiently. Based on these findings, the researchers now hope to jointly develop novel approaches to fight viral infectious agents and tumor diseases.
Prof. Dr. Michael Schindler
+49 7071 29-87459
Businger et al., Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via pUL97, www.nature.com/articles/s41564-019-0557-8
Deutschmann et al., A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1, www.nature.com/articles/s41564-019-0529-z
Bianca Hermle | idw - Informationsdienst Wissenschaft
When added to gene therapy, plant-based compound may enable faster, more effective treatments
18.10.2019 | Scripps Research Institute
Diabetes: A next-generation therapy soon available?
17.10.2019 | Université de Genève
A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)
It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...
Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.
The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...
Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.
Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...
A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.
The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...
Superconductivity has fascinated scientists for many years since it offers the potential to revolutionize current technologies. Materials only become superconductors - meaning that electrons can travel in them with no resistance - at very low temperatures. These days, this unique zero resistance superconductivity is commonly found in a number of technologies, such as magnetic resonance imaging (MRI).
Future technologies, however, will harness the total synchrony of electronic behavior in superconductors - a property called the phase. There is currently a...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
18.10.2019 | Power and Electrical Engineering
18.10.2019 | Medical Engineering
18.10.2019 | Physics and Astronomy