tetano
Editor, Senior Moderator
J Med Virol
. 2023 Mar 20.
doi: 10.1002/jmv.28686. Online ahead of print.
Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection
Denisa Bojkova[SUP] 1 [/SUP], Marco Bechtel[SUP] 1 [/SUP], Tamara Rothenburger[SUP] 1 [/SUP], Joshua D Kandler[SUP] 1 [/SUP], Lauren Hayes[SUP] 2 [/SUP], Ruth Olmer[SUP] 3 [/SUP], Ulrich Martin[SUP] 3 [/SUP], Danny Jonigk[SUP] 4 5 [/SUP], Sandra Ciesek[SUP] 1 6 7 [/SUP], Mark N Wass[SUP] 2 [/SUP], Martin Michaelis[SUP] 2 [/SUP], Jindrich Cinatl Jr[SUP] 1 8 [/SUP]
Affiliations
Abstract
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. This article is protected by copyright. All rights reserved.
Keywords: BA.1; BA.5; COVID-19; Delta; SARS-CoV-2; antiviral state; influenza; interferon; monocytes; super-infection.
. 2023 Mar 20.
doi: 10.1002/jmv.28686. Online ahead of print.
Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection
Denisa Bojkova[SUP] 1 [/SUP], Marco Bechtel[SUP] 1 [/SUP], Tamara Rothenburger[SUP] 1 [/SUP], Joshua D Kandler[SUP] 1 [/SUP], Lauren Hayes[SUP] 2 [/SUP], Ruth Olmer[SUP] 3 [/SUP], Ulrich Martin[SUP] 3 [/SUP], Danny Jonigk[SUP] 4 5 [/SUP], Sandra Ciesek[SUP] 1 6 7 [/SUP], Mark N Wass[SUP] 2 [/SUP], Martin Michaelis[SUP] 2 [/SUP], Jindrich Cinatl Jr[SUP] 1 8 [/SUP]
Affiliations
- PMID: 36938992
- DOI: 10.1002/jmv.28686
Abstract
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. This article is protected by copyright. All rights reserved.
Keywords: BA.1; BA.5; COVID-19; Delta; SARS-CoV-2; antiviral state; influenza; interferon; monocytes; super-infection.