Coronavirus hijacks antiviral immune factors

SARS-CoV-2 uses interferon-induced transmembrane proteins for effective infection

09-Aug-2021 - Germany

How does the coronavirus SARS-CoV-2 manage to spread so effectively in the body? One of the reasons is that it turns original "opponents" into "helpers". Scientists at the University Hospital in Ulm have shown in a study that SARS-CoV-2 uses so-called interferon-induced transmembrane proteins (IFITMs) to penetrate host cells more effectively. IFITMs are actually known for their antiviral effect. The Ulm researchers have now been able to show that SARS-CoV-2 "misuses" these transmembrane proteins, making it even more infectious.

The coronavirus uses a broad range of sophisticated strategies to trick the human immune system. This is the only way that SARS-CoV-2 is able to effectively infect humans and spread rapidly. Researchers at Ulm University Hospital have now discovered that the virus responsible for the COVID-19 pandemic "hijacks" certain membrane proteins and uses them for its own replication. These proteins are known as interferon-induced transmembrane proteins (IFITMs), which are known to keep various viral pathogens, such as HIV or influenza viruses, in check. The Ulm study shows that SARS-CoV-2 uses IFITMs to effectively infect human cells. The results were published in Nature Communications.

"We were very surprised by these results. After all, interferon-induced transmembrane proteins were previously known more for their antiviral effect," says Professor Frank Kirchhoff. The head of the Institute of Molecular Virology at the University Hospital in Ulm is the senior author of the study. The Ulm data are supposedly at odds with results from other research groups that reported that IFITM proteins inhibit human coronaviruses. "However, the apparent contradictions can be explained," Dr. Konstantin Sparrer points out. The scientist heads a BMBF junior research group at the Institute of Molecular Virology and also played a leading role in the study. "Previous results - which we were able to confirm experimentally, by the way - were obtained under very artificial conditions. For example, IFITMs were artificially overexpressed and so-called pseudovirions were mostly used," Kirchhoff explains, adding "However, when cells from relevant human tissues such as lung, heart or intestine are infected with real SARS-COV-2, IFITMs increase viral infection and production of infectious viruses by several orders of magnitude. We were able to show this in our study as well."

The study, which also involved international cooperation partners and numerous other researchers at Ulm University Medical Centre, used experimental conditions that have greater physiological relevance than previously used systems. For example, primary lung, heart and intestinal cells as well as organoids were used. In severe courses, the lungs, heart and intestine are among the main targets of SARS-CoV-2 infection. Organoids are artificial 3D mini-organs that replicate the real situation - for example in the intestine - better than conventional cell cultures.

The researchers also found the first evidence of the amplifying mechanism. "Using high-performance microscopic imaging and highly sensitive interaction assays, we were able to demonstrate that the spike protein of SARS-CoV-2 interacts with and exploits IFITMs, which promotes virus entry," Caterina Prelli Bozzo and Rayhane Nchioua - both first authors of the study - sum up the findings. Conversely, the scientists were able to show that infection proceeds far less efficiently when the production of these membrane proteins is experimentally suppressed.

The unexpected finding that IFITMs are cofactors of effective SARS-CoV-2 infection also has therapeutic potential. "Blocking IFITMs with antibodies inhibits infection of human lung, heart and intestinal cells," the researchers report. Furthermore, the result helps to explain why this coronavirus can spread so efficiently: among other things, by misusing interferon-induced transmembrane proteins, which normally have an antiviral effect, for its own purposes.

Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.

Original publication

Caterina Prelli Bozzo, Rayhane Nchioua, Meta Volcic, Lennart Koepke, Jana Krüger, Desiree Schütz, Sandra Heller, Christina M. Stürzel, Dorota Kmiec, Carina Conzelmann, Janis Müller, Fabian Zech, Elisabeth Braun, Rüdiger Groß , et al.; "IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro"; Nature Communications (2021) 12:4584

https://www.bionity.com/en/news/1172247/coronavirus-hijacks-antiviral-immune-factors.html