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Influenza viruses from bats use a completely different access route into the cell than all previously known influenza types / Can also infect human cells in the laboratory / Publication in Nature

Researchers at the University Medical Center Fribourg and the University of Zurich have discovered a completely new infection pathway for influenza viruses. An influenza type discovered in bats infects human and animal cells by binding to the surface complex MHC-II and not to sialic acid like all previously known influenza viruses. As the immune protein MHC-II is very similar in many animal species and humans, the discovery plays an important role in assessing the infection risk and potential danger of the virus type. The study, which was published in the journal Nature on February 20, 2019, also provides new approaches to the evolutionary development of influenza viruses.

"In the laboratory, bat viruses can use the MHC-II complexes of mice, pigs, chickens or humans for cell entry. Natural transmission of these influenza viruses from bats to other vertebrates and even humans can therefore not be ruled out," says Prof. Dr. Martin Schwemmle, study and research group leader at the Institute of Virology at the Freiburg University Medical Center.

Gene expression analysis and gene scissors lead to success

With a dual strategy and a great deal of effort, the Freiburg and Zurich researchers finally succeeded in identifying the cellular factor for virus entry into the cell. On the one hand, the Zurich researchers led by Prof. Dr. Silke Sterz from the Institute of Medical Virology at the University of Zurich compared which proteins are produced in infectious versus non-infectious cells. In this so-called gene expression analysis, in which the quantity of proteins is estimated via mRNA copies, there was already much evidence of the MHC-II complex.

In addition, the Freiburg researchers in Prof. Schwemmle's group cut one of a total of 20,000 genes in individual animal cells using the CRISPR-Cas gene scissors in countless experiments. "Cells in which we switched off MHC-II became immune to infection. This was proof that the virus enters the cell with the help of MHC-II," says the virologist.

The emergence of a second infection mechanism also raises the question for the researchers as to which type is older in evolutionary terms. "It is quite possible that the infection pathway via MHC-II that has now been discovered originally evolved from the sialic acid pathway that we know," says Prof. Schwemmle.

The study gives rise to many new research questions: Are there other influenza viruses that use the previously unknown host cell receptor? How easily can influenza viruses switch receptors and is it possible for influenza viruses to develop that infect target cells via both receptors? "These are all questions that we now want to investigate. Because influenza viruses are obviously much more versatile than previously thought," says virologist Prof. Schwemmle.

Original title of the publication: MHC class II proteins are cross-species entry receptors for bat influenza viruses

DOI: 10.1038/s41586-019-0955-3

Link to the study: https://www.nature.com/articles/s41586-019-0955-3

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