PT  - JOURNAL ARTICLE
AU  - Wang, Chang
AU  - Honce, Rebekah
AU  - Salvatore, Mirella
AU  - Yang, Jianjun
AU  - Twells, Nicholas M.
AU  - Mahal, Lara K.
AU  - Schultz-Cherry, Stacey
AU  - Ghedin, Elodie
TI  - Reduced inflammatory response and promoted multiciliated cell differentiation in mice protected by defective interfering influenza virus
AID  - 10.1101/2022.01.25.477719
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.25.477719
4099  - http://biorxiv.org/content/early/2022/01/25/2022.01.25.477719.short
4100  - http://biorxiv.org/content/early/2022/01/25/2022.01.25.477719.full
AB  - Influenza defective interfering (DI) viruses have long been considered promising antiviral candidates because of their ability to interfere with replication-competent viruses and to induce antiviral immunity. However, the mechanisms underlying DI-mediated antiviral immunity have not been extensively explored. Here, we demonstrated interferon (IFN) independent protection conferred by influenza DI virus against homologous virus infection in mice deficient in type I and III IFN signaling. By integrating transcriptional and post-transcriptional regulatory data we identified unique host signatures in response to DI co-infection. DI-treated mice exhibited reduced viral transcription, less intense inflammatory and innate immune responses, and primed multiciliated cell differentiation in their lungs at an early stage of infection, even in the absence of type I or III IFNs. Overall, our study provides mechanistic insight into the protection mediated by DIs, implying a unifying theme involving inflammation and multiciliogenesis in maintaining respiratory homeostasis, and reveals their IFN-independent antiviral activity.Competing Interest StatementThe authors have declared no competing interest.