Most people get herpes viruses in childhood. After a single infection, viruses remain in the body for life. Eight known human herpesviruses include the herpes simplex virus that causes known mouth blisters, varicella-zoster virus that causes smallpox and shingles, and Epstein-Barr virus, which causes glandular fever and also contributes to the development of many cancers. Although herpesvirus infections do not significantly affect the health of most people, patients with severe immune system damage, such as transplant patients, have difficulty controlling the virus. This can lead to reactions to rejection and serious organ damage, including death.
TRIM43 inhibits the proliferation of herpes viruses
To address the risks of herpes viruses, scientists at the Erlangen University Institute of Virology are looking for endogenous proteins that can keep viruses in the bay. "We are interested in so-called Internal Immune Response, protein molecules that can prevent virus multiplication right in cells," Dr. copper. Full. The research team discovered so-called TRIM proteins. TRIM means "tripartite motif", a three-part protein motif that can bind other proteins and cause their degradation. One of the TRIM proteins of the previously described TRIM43 has been shown to cause degradation of another cellular protein called pericentrin. The breakdown of pericentrine leads to changes in kernel architecture and thus inhibits the proliferation of herpes viruses. TRIM43 was active against all herpesviruses tested in the study.
Hope for new therapies
It is remarkable that cells produce very large amounts of TRIM43 in response to viral infection. "In normal cells, TRIM43 is almost undetectable, but after the virus infection is a cell full of proteins," Dr. Full. In co-operation with dr. Klaus Korn, Head of Viral Diagnostics at the Virology Institute and prof. Dr. copper. Michael Sturzl, head of Molecular and Experimental Surgery at the Surgical Clinic (Prof. Dr. Robert Grützmann) at the University Hospital Erlangen, showed the research team that the increase in TRIM43 protein in patients with acute herpesvirus infection and even herpes virus-bearing tumor cells is detectable. "This proves that TRIM43 plays a role in human infection and raises the hope that new therapies for herpesviruses could be developed based on the results," concluded Florian Full.
Moreover, the group of researchers has shown that TRIM43 production in response to viral infection is dependent on the DUX4 gene, which is normally only active in very early embryonic development. Why a herpesvirus infection leads to activation of the embryonic gene DUX4 and whether it is a generally unknown immune response against viruses is the subject of a new research project at the University of Erlangen, the Interdisciplinary Center for Clinical Research in Medicine Friedrich-Alexander-University Erlangen-Nuremberg Faculty within the subproject two and a half years.
The scientific work was done by Dr. copper. Florian Plná in the laboratory prof. Dr. Copper. Michaela Gacková (Harvard University, Boston, USA and Chicago University of Chicago, USA) and is in the laboratory of prof. Dr. Copper. Institute of Virology, Erlangen University Hospital. Armin Ensser continued.
Dr. Florian Plná
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