Nav: Home

Researchers discover new portal of entry for influenza viruses

March 04, 2019

Researchers from the Medical Center - University of Freiburg and the University of Zurich have discovered an entirely new infection route for influenza A viruses. While all previously known influenza A viruses bind sialic acid moieties on the host cell surface, the recently discovered bat-derived influenza A virus subtypes infect human and animal cells by utilizing MHC class II proteins. The immunologically relevant MHC class II molecules are ubiquitously found in many animal species, which is why the discovery will play an important role in assessing the risk of spill-over infections to other species than bats. The study, published on 20 February 2019 in the journal Nature, also provides new approaches to the evolutionary genesis of influenza viruses.

"In the lab, bat viruses can use the MHC class II complexes of mice, pigs, chickens, or humans to enter the cell. It is thus not unlikely that these bat-derived influenza viruses could be transmitted naturally from bats to other vertebrates and even humans," says Prof. Dr. Martin Schwemmle, study and research group leader at the Institute of Virology at the University Medical Center Freiburg.

Gene Expression Analysis and Gene Scissors Lead to Success

With a two-pronged strategy and a lot of effort, the researchers from Freiburg and Zurich finally succeeded in finding the cellular factor mediating the virus's entry into the host cell. First, the group of Prof. Dr. Silke Sterz from the Institute of Medical Virology of the University of Zurich compared the proteins produced in infectible cells to those produced in non-infectible cells. Using a technique called transcriptomic profiling, the researchers estimated the amount of cellular proteins via mRNA copies. This approach already provided strong indications for the MHC class II complex as the receptor candidate. Then, the team from Freiburg led by Prof. Schwemmle conducted a screening experiment in which they cut one of a total of 20,000 genes in single cells using the molecular scissor CRISPR-Cas. "Cells in which we switched off MHC class II were immune to infection. That was the final proof that the virus enters the cell with the help of MHC class II molecules," says the virologist.

The discovery of this second, sialic acid-independent, mechanism also raises the question which strategy was first in evolutionary terms. "It is quite possible that the newly discovered route of infection via MHC class II originates from the already known sialic acid pathway," says Prof. Schwemmle. The current study also raises new research questions: Are there other influenza viruses that use MHC class II proteins as host cell receptor? How simple can influenza viruses switch their receptors, and is it even possible that influenza viruses emerge, which can infect target cells by both receptors? "These are all questions that we now aiming to investigate, because influenza viruses are evidently more versatile than previously thought," says the virologist Prof. Schwemmle.
-end-
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

Contact:

Prof. Dr. Martin Schwemmle
Research Group Leader
Institute of Virology
Medical Center - University of Freiburg
Phone: +49 (0)761 203-6526
martin.schwemmle@uniklinik-freiburg.de

University of Freiburg

Related Influenza Articles:

How proteins help influenza A bind and slice its way to cells
Researchers have provided new insight on how two proteins help influenza A virus particles fight their way to human cells.
Eating elderberries can help minimize influenza symptoms
Conducted by Professor Fariba Deghani, Dr. Golnoosh Torabian and Dr.
Mechanism to form influenza A virus discovered
A new study by Maria João Amorim's team, from the Gulbenkian Institute of Science, now reveals where the genomes of the influenza A virus are assembled inside infected cells.
Bat influenza viruses could infect humans
Bats don't only carry the deadly Ebola virus, but are also a reservoir for a new type of influenza virus.
New VaxArray publication on influenza neuraminidase quantification
InDevR Inc. announced publication of 'A Neuraminidase Potency Assay for Quantitative Assessment of Neuraminidase in Influenza Vaccines' in npj Vaccines.
More Influenza News and Influenza Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...