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Omicron‐induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection

Bojkova, Denisa, Bechtel, Marco, Rothenburger, Tamara, Kandler, Joshua D., Hayes, Lauren, Olmer, Ruth, Martin, Ulrich, Jonigk, Danny, Ciesek, Sandra, Wass, Mark N., and others. (2023) Omicron‐induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection. Journal of Medical Virology, 95 (3). Article Number e28686. ISSN 1096-9071. (doi:10.1002/jmv.28686) (KAR id:100643)


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 cultures of primary human bronchial epithelial cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active types 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 signaling was mediated via double‐stranded RNA recognition by MDA5, as MDA5 knockout 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 signaling. 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.

Item Type: Article
DOI/Identification number: 10.1002/jmv.28686
Uncontrolled keywords: Antiviral state, BA.1, BA.5, COVID‐19, Delta, influenza, interferon, monocytes, SARS‐CoV‐2, super‐infection
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 28 Mar 2023 10:36 UTC
Last Modified: 14 Apr 2023 14:58 UTC
Resource URI: (The current URI for this page, for reference purposes)

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