Most people acquire herpesviruses as early as childhood. After a single infection, the viruses remain in the body for the rest of their lives. Eight known human herpesviruses include the herpes simplex virus that causes known bladders around the mouth, the varicella zoster virus that causes chicken pox and shingles, and the Epstein-Barr virus that causes glandular fever. and is also involved in the development of many cancers. Although herpes infections do not significantly affect the health of most people, patients with severely compromised immune systems, such as after transplantation, have difficulty controlling the virus. This can lead to rejection reactions and severe organ damage, including death.
TRIM43 inhibits the herpes virus proliferation
To counteract the risks associated with herpes viruses, scientists at the Virology Institute of the University Hospital Erlangen are looking for endogenous proteins that can stop viruses. "We are interested in the so-called Inner immune response, protein molecules that can prevent the multiplication of viruses directly in cells" – explained Dr. med. Peł. The research team discovered so-called TRIM proteins. TRIM stands for a "tripartite theme", a three-part protein motif that can bind other proteins and cause them to degrade. It was shown that one of the TRIM proteins, previously unspecified TRIM43, causes the degradation of another cellular protein called pericentrin. Disintegration of pericentrin leads to changes in the architecture of the testis, and thus inhibits the proliferation of herpes viruses. TRIM43 was active against all herpes viruses tested in the study.
Hope for new therapies
Surprisingly, the cells produce very large amounts of TRIM43 in response to a viral infection. "In normal TRIM43 cells, it is almost undetectable, but after a viral infection the cell is full of protein" Dr. Full. In cooperation with dr. Klaus Korn, Head of Viral Diagnostics at the Virological Institute and prof. Dr. med. Michael Stürzl, head of molecular and experimental surgery at the surgical clinic (director: Prof. Dr. Robert Grützmann) from University Hospital Erlangen, showed the research team that the increase in TRIM43 protein in samples of patients with acute herpesvirus infection and even in cancer cells carrying herpes virus are detectable. "This proves that TRIM43 plays a role in human infection and raises the hope that it will be possible to develop new therapies for herpes viruses based on results," concludes Florian Full.
In addition, a team of scientists has shown that the production of TRIM43 in response to a viral infection depends on DUX4, a gene that under normal conditions is active only at a very early stage of embryonic development. Why the herpes virus infection leads to the activation of the embryonic DUX4 gene, and whether it is a hitherto unknown immune response against viruses, is the subject of a new research project at the University of Erlangen, Interdisciplinary Center for Clinical Research at the Medical University Friedrich-Alexander-University Erlangen-Nürnberg as part of subproject for two and a half years.
The scientific work was done by Dr. med. Florian Peł in the laboratory of prof. Dr. Med. Michaela Gack (Harvard University, Boston, USA and the University of Chicago, Chicago, USA) and is at the Virology Institute of the University Hospital Erlangen in the laboratory of prof. Dr. Med. Armin Ensser continued.
Dr. Florian Full
Tel .: 09131 85-26494