TY  - INPR
A1  - Bojkova, Denisa
A1  - Bechtel, Marco
A1  - Rothenburger, Tamara
A1  - Kandler, Joshua D.
A1  - Hayes, Lauren
A1  - Olmer, Ruth Maria
A1  - Martin, Ulrich
A1  - Jonigk, Danny David
A1  - Ciesek, Sandra
A1  - Wass, Mark N.
A1  - Michaelis, Martin
A1  - Cinatl, Jindrich
T1  - Omicron-induced interferon signalling prevents influenza A virus infection
T2  - bioRxiv
N2  - Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (α/β) and III (λ) interferons and protected cells from super-infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza-like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron-induced interferon signalling was mediated via double-stranded RNA recognition by MDA5, as MDA5 knock-out prevented it. The JAK/ STAT inhibitor baricitinib inhibited the Omicron-mediated antiviral response, suggesting it is caused by MDA5-mediated interferon production, which activates interferon receptors that then trigger JAK/ STAT signalling. In conclusion, our study 1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, 2) shows that Omicron infection protects cells from influenza A virus super-infection, and 3) indicates that BA.1 and BA.5 induce comparable antiviral states.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73090
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-730904
IS  - 2022.09.06.506799
ER  -