RT Journal Article
SR Electronic
T1 Reduced inflammatory response and promoted multiciliated cell differentiation in mice protected by defective interfering influenza virus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.25.477719
DO 10.1101/2022.01.25.477719
A1 Chang Wang
A1 Rebekah Honce
A1 Mirella Salvatore
A1 Jianjun Yang
A1 Nicholas M. Twells
A1 Lara K. Mahal
A1 Stacey Schultz-Cherry
A1 Elodie Ghedin
YR 2022
UL http://biorxiv.org/content/early/2022/01/25/2022.01.25.477719.abstract
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.