Infections such as with human cytomegalovirus and a certain type of human polyomavirus frequently cause complications in transplant recipients. For these patients it would therefore be particularly beneficial to have substances that suppress the immune system and exert an antiviral activity at the same time – thus killing two birds with one stone.
Jointly with colleges from Heidelberg University Hospital of Internal Medicine, researchers Professors Karin and Felix Hoppe-Seyler of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now tested a number of drugs with such an activity profile. They also tested the substances in liver cells infected with hepatitis B viruses (HBV) in the culture dish. The result: Liver cells that had been treated even produced considerably more viral offspring than untreated ones.
The substances under investigation inhibit the synthesis of nucleotides, which are the basic building blocks of DNA. This is how they exert their immunosuppressive effect: They slow down multiplication of immune cells because these lack building material for duplicating their genetic material. "The lack of DNA building blocks can cause a kind of stress in specific cells, which shows in the activation of a stress protein called p38", says Felix Hoppe-Seyler. "In liver cells, p38 very effectively activates the replication of hepatitis B viruses. "
The findings of the DKFZ researchers are a definite indication that administering these drugs in transplant recipients bears risks. Liver transplants, in particular, often have to be done because the body's own organ has been destroyed by hepatitis B viruses. In such cases, drug-induced activation of remaining HBV in the body may lead to the donor organ being attacked by hepatitis B viruses again.Felix Hoppe-Seyler suspects that besides the three substances the group has investigated there are other substances which also cause an activation of p38. "In cancer patients being treated by chemotherapy, there is often a reactivation of chronic HBV infections. This has always been put down to their weakened immune system. We will now investigate whether this may also be due to activation of stress protein p38," said the virologist outlining the goals of his further research.
Karin Hoppe-Seyler, Peter Sauer, Claudia Lohrey and Felix Hoppe-Seyler: The Inhibitors of Nucleotide Biosynthesis Leflunomide, FK778, and Mycophenolic Acid Activate Hepatitis B Virus Replication In Vitro. Hepatology, 2012, DOI: 10.1002/hep.25602
A picture for this press release is available at: http://www.dkfz.de/de/presse/pressemitteilungen/2012/images/hbv-partikel-sw.jpg
Picture caption: Electron microscopic picture of hepatitis B viruses. Thomas Bock, Hanswalter Zentgraf, German Cancer Research Center.
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg where promising approaches from cancer research are translated into the clinic. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. The center is a member of the Helmholtz Association of National Research Centers. Ninety percent of its funding comes from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.
Dr. Sibylle Kohlstädt | EurekAlert!
New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego
Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
17.01.2018 | Ecology, The Environment and Conservation
17.01.2018 | Physics and Astronomy
17.01.2018 | Awards Funding