Omicron-induced interferon signalling prevents influenza A virus infection
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.
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Lok-Yin Roy Wong
Review 2: "Omicron-induced interferon signalling prevents influenza A virus infection"
The authors demonstrate differential interferon-signaling in SARS-CoV-2 Delta and Omicron variants, which is correlated with the ability of Omicron infection, but not Delta infection, to protect in vitro cell cultures from subsequent influenza A virus co-infection.
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Dennis Metzger, Tarani Kanta Barman
Review 1: "Omicron-induced interferon signalling prevents influenza A virus infection"
The authors demonstrate differential interferon-signaling in SARS-CoV-2 Delta and Omicron variants, which is correlated with the ability of Omicron infection, but not Delta infection, to protect in vitro cell cultures from subsequent influenza A virus co-infection.
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Strength of evidence
Reviewers: Dennis Metzger (Albany Medical College), Tarani Kanta Barman (University of Texas Medical Branch) | 📘📘📘📘📘
Lok-Yin Roy Wong (University of Iowa) | 📗📗📗📗◻️ -
