Omicron-induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection
© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
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| Enthalten in: |
Journal of medical virology - 95(2023), 3 vom: 04. März, Seite e28686 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bojkova, Denisa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.03.2023 Date Revised 19.06.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.28686 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Omicron-induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection |
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| 520 | |a © 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BA.1 | |
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| 650 | 4 | |a COVID-19 | |
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| 700 | 1 | |a Bechtel, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Rothenburger, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Kandler, Joshua D |e verfasserin |4 aut | |
| 700 | 1 | |a Hayes, Lauren |e verfasserin |4 aut | |
| 700 | 1 | |a Olmer, Ruth |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Jonigk, Danny |e verfasserin |4 aut | |
| 700 | 1 | |a Ciesek, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Wass, Mark N |e verfasserin |4 aut | |
| 700 | 1 | |a Michaelis, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Cinatl, Jindrich |c Jr |e verfasserin |4 aut | |
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