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In human cells, the genetic material, the DNA, is wrapped around special histone proteins. By making changes to these histones, individual genes can be specifically switched on or off. Unlike the genetic material, these histone changes can be altered by drugs. A team of researchers from the Institute of Virology at the Freiburg University Medical Center, together with colleagues from Switzerland, the USA and China, has now shown for the first time that such a histone-like code for regulating the reading pattern also exists in viruses. The researchers hope that this will enable them to specifically inhibit the replication of influenza A viruses in the future and thus avert severe courses of the viral infection. The study was published in advance in the online edition of the journal Nature Communications on November 2, 2017.

"We have shown that there is a comprehensive code that controls, among other things, the transcription of the viral genetic material. This is a decisive step towards new therapeutic approaches," says Prof. Dr. Martin Schwemmle, research group leader at the Institute of Virology at the Freiburg University Medical Center and head of the study. The researchers have already succeeded in preventing the virus from replicating by changing the reading pattern. However, these changes were permanent and not suitable for therapy. "Next, we need to decipher how the reading pattern of the viral genetic material is altered under natural conditions. Then we may be able to intervene here and stop the virus," adds Prof. Schwemmle.

To change the reading pattern of the influenza A genome, acetyl residues are attached to the packaging proteins - so-called viral nucleoproteins (NP). In order to investigate the significance of this acetylation, the Freiburg researchers generated virus types that feigned either permanent acetylation or non-acetylation at certain positions. This showed that different steps in the viral replication cycle are blocked depending on the respective position of the forced change.

"However, it is still too early to make a precise statement about the interaction of the various changes to the nucleoproteins, including acetylation," says Prof. Schwemmle. Only a complete decoding of the nucleoprotein code will reveal the significance of these changes for the replication of influenza A viruses.

Original title of the publication: Role of influenza A virus NP acetylation on viral growth and replication

DOI: 10.1038/s41467-017-01112-3

Link to the publication: www.nature.com/articles/s41467-017-01112-3

Contact: 
Prof. Dr. Martin Schwemmle 
Research Group Leader 
Institute of Virology 
University Medical Center Freiburg 
Phone: 0761 203-6526 
martin.schwemmle@uniklinik-freiburg.de