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
Mutations in donors' stem cells may cause problems for cancer patients
17.01.2020 | Washington University School of Medicine
Overactive brain waves trigger essential tremor
17.01.2020 | Columbia University Irving Medical Center
Styrofoam or copper - both materials have very different properties with regard to their ability to conduct heat. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz and the University of Bayreuth have now jointly developed and characterized a novel, extremely thin and transparent material that has different thermal conduction properties depending on the direction. While it can conduct heat extremely well in one direction, it shows good thermal insulation in the other direction.
Thermal insulation and thermal conduction play a crucial role in our everyday lives - from computer processors, where it is important to dissipate heat as...
In order to advance the transfer of research developments from the field of quantum sensor technology into industrial applications, an application laboratory is being established at Fraunhofer IAF. This will enable interested companies and especially regional SMEs and start-ups to evaluate the innovation potential of quantum sensors for their specific requirements. Both the state of Baden-Württemberg and the Fraunhofer-Gesellschaft are supporting the four-year project with one million euros each.
The application laboratory is being set up as part of the Fraunhofer lighthouse project »QMag«, short for quantum magnetometry. In this project, researchers...
Microtubules, filamentous structures within the cell, are required for many important processes, including cell division and intracellular transport. A...
Researchers from the University Hospital Zurich, ETH Zurich, Wyss Zurich and the University of Zurich have developed a machine that repairs injured human livers and keep them alive outside the body for one week. This breakthrough may increase the number of available organs for transplantation saving many lives of patients with severe liver diseases or cancer.
Until now, livers could be stored safely outside the body for only a few hours. With the novel perfusion technology, livers - and even injured livers - can now...
A balloon-borne scientific instrument designed to study the origin of cosmic rays is taking its second turn high above the continent of Antarctica three and a half weeks after its launch.
SuperTIGER (Super Trans-Iron Galactic Element Recorder) is designed to measure the rare, heavy elements in cosmic rays that hold clues about their origins...
16.01.2020 | Event News
15.01.2020 | Event News
07.01.2020 | Event News
17.01.2020 | Life Sciences
17.01.2020 | Power and Electrical Engineering
17.01.2020 | Life Sciences