Omicron-induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection.
J Med Virol
; 95(3): e28686, 2023 03.
Article
en En
| MEDLINE
| ID: mdl-36938992
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 cultures of primary human bronchial epithelial cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active types I (α/ß) 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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Virus de la Influenza A
/
Gripe Humana
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Subtipo H1N1 del Virus de la Influenza A
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Subtipo H5N1 del Virus de la Influenza A
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Inhibidores de las Cinasas Janus
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COVID-19
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Med Virol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania