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Using the body’s own proteins to fight herpes

The researchers Prof. Ensser (r.) and Dr. Full (Photo: Luise Laufer/Universitätsklinikum Erlangen)

Scientists in Erlangen find new anti-viral mechanism against herpes

When we are infected by a virus, our body detects this attack and starts a series of defensive reactions. In collaboration with researchers at the University of Chicago, USA, a team of researchers led by Dr. Florian Full and Prof. Dr. Armin Ensser at the Institute of Clinical and Molecular Virology have now discovered a new defensive reaction against herpes viruses. “Our results describe a previously unknown mechanism in the body for fighting herpes viruses”, says Dr. Full. The researchers have now published their findings in the latest issue of the renowned journal ‘Nature Microbiology’.

Most people are infected by herpes viruses in early childhood. After a single infection, the viruses remain in the body for life. The eight known human herpes viruses include herpes-simplex, which causes the familiar blisters around the mouth, varicella zoster virus, which causes chickenpox and shingles, and the Epstein-Barr virus that causes glandular fever and is involved in the development of particular forms of cancer. Although infections with herpes viruses do not cause long-term health problems for most people, patients with severely compromised immune systems, such as after transplants, often have problems controlling the viruses. This can lead to organ rejection, serious organ damage and even death.

TRIM43 inhibits the proliferation of herpes viruses

To counteract the risks of herpes viruses, scientists from the Institute of Clinical and Molecular Virology are searching for proteins in the body that can keep the viruses in check. “We are interested in the so-called intrinsic immune response, that is, molecules of protein that can prevent the growth of viruses directly in the cells”, explains Dr. Full. The team of researchers found what they were looking for in so-called TRIM proteins. TRIM stands for ‘tripartite motif’, a three-part protein motif that can bind other proteins and cause their degradation. The scientists demonstrated that one of the TRIM proteins, the previously unknown TRIM43, causes the breakdown of another cellular protein called pericentrin. The breakdown of pericentrin leads to changes in the architecture of the nucleus and thus limits the proliferation of the herpes viruses. TRIM43 was active against all herpes viruses tested in the study.

Hope for new therapies

What was remarkable was the fact that the cells produce very large quantities of TRIM43 in response to the viral infection. “TRIM43 is almost undetectable in normal cells, but they are full of this protein after a viral infection”, says Dr. Full. In collaboration with Dr. Klaus Korn, head of Virus Diagnostics at the Institute, and Prof. Dr. Michael Stürzl, head of Molecular and Experimental Surgery at the Department of Surgery, the research team was able to detect an increase in the TRIM43 protein in patient samples with acute herpes virus infections and even in tumor cells that carry a herpes virus. “This proves that TRIM43 plays a role in infections in humans and raises the hope that it could be possible to develop new therapies against herpes viruses based on these results”, Dr. Full concludes.

In addition, the research team also demonstrated that the production of TRIM43 as a response to a viral infection is dependent on DUX4, a gene that is usually only active during the very early stages of embryo development. Why an infection with herpes viruses leads to the activation of the embryonic gene DUX4 and whether it is just generally a previously unknown immune response to viruses is the subject of a new research project at Universitätsklinikum Erlangen that is being funded for two and a half years by the Interdisciplinary Center for Clinical Research as part of a sub-project.

The scientific work was started by Dr. Full in the laboratory of Prof. Dr. Michaela Gack (Harvard University, Boston, USA and University of Chicago, Chicago, USA) and is being continued in the laboratory of Prof. Dr. Ensser at the Institute of Clinical and Molecular Virology.

Further information

Dr. Florian Full
Phone.: +49 9131 85-26494