Influenza defective interfering virus promotes multiciliated cell differentiation and reduces the inflammatory response in mice
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ABSTRACT:
PROVIDER: PRJNA777796 | ENA |
REPOSITORIES: ENA
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Project description: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. This increased multiciliogenesis could also be detected at the protein level by immunofluorescence staining of lung tissue from DI-treated mice. 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.
2023-05-15 | GSE188122 | GEO
Project description:Influenza defective interfering (DI) viruses have long been considered promising antiviral candidates because of their ability to interfere with replication-competent viruses and induce antiviral immunity. However, the mechanisms underlying DI-mediated antiviral immunity have not been extensively explored. Here, we demonstrated the interferon (IFN)-independent protection conferred by the influenza DI virus against homologous virus infection in mice deficient in type I and III IFN signaling. We identified unique host signatures responding to DI coinfection by integrating transcriptional and posttranscriptional regulatory data. 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. This increased multiciliogenesis could also be detected at the protein level via the immunofluorescence staining of lung tissue from DI-treated mice. 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 revealing their IFN-independent antiviral activity. IMPORTANCE During replication, the influenza virus generates genetically defective viruses. These are found in natural infections as part of the virus population within the infected host. Some versions of these defective viruses are thought to have protective effects through their interference with replication-competent viruses and induction of antiviral immunity. To better determine the mechanisms underlying the protective effects of these defective interfering (DI) viruses, we tested a DI that we previously identified in vitro with mice. Mice that were infected with a mix of wild-type influenza and DI viruses had less intense inflammatory and innate immune responses than did mice that were infected with the wild-type virus only, even when type I or III interferons, which are cytokines that play a prominent role in defending the respiratory epithelial barrier, were absent. More interestingly, the DI-infected mice had primed multiciliated cell differentiation in their lungs, indicating the potential promotion of epithelial repair by DIs.
| S-EPMC10308934 | biostudies-literature
Project description:Parasitic elements of the viral population which are unable to replicate on their own yet rise to high frequencies, defective interfering particles are found in a variety of different viruses. Their presence is associated with a loss of population fitness, both through the depletion of key cellular resources and the stimulation of innate immunity. For influenza A virus, these particles contain large internal deletions in the genomic segments which encode components of the heterotrimeric polymerase. Using a library-based approach, we comprehensively profile the growth and replication of defective species, demonstrating they possess an advantage during genome replication, and that exclusion during packaging reshapes population composition in a manner consistent with their final, observed, distribution in natural populations. We find that innate immunity is not linked to the size of a deletion; however, replication of defective segments can enhance their immunostimulatory properties. Overall, our results address several key questions in defective influenza A virus biology, and the methods we have developed to answer those questions may be broadly applied to other defective viruses.
2021-11-17 | GSE183442 | GEO
Project description:To determine what genes are upregulated in multiciliated cells, we manipulated Xenopus laevis ectoderm to either make more or fewer of this cell type with multiple approaches across multiple timepoints. By finding differentially expressed genes in common across all comparisons in which multiciliated cell number changed, we obtained a robust, but conservative, core group of multiciliated cell genes.
2015-12-25 | GSE76342 | GEO
Project description:Multiciliated cells (MCCs) possess multiple motile cilia on the cell surface and are widely distributed throughout the vertebrate body to perform important physiological functions by regulating fluid movement in the intercellular space. However, neither their function during organ development nor the molecular mechanisms underlying multiciliogenesis are yet well understood. We aim to study the function of miR-34b in multiciliogenesis. We used microarrays to study the global gene expression change in multiciliated cells after miR-34b knockdown. Multiciliated cells were isolated from 3 dpf control embryos (injected with control morpholino) and miR-34b morphants (injected with miR-34b morpholino) for RNA extraction and hybridization on Affymetrix microarrays. Two independent sets of biological replicates were used.
2013-05-11 | E-GEOD-46844 | biostudies-arrayexpress
Project description:Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. The kinetics and efficiency of sgRNAs production during viral replication in different cell types or sgRNA transcription by individual viral strains or variants are yet to be studied to shed light on fundamental mechanisms necessary for viral replication. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study a growing number of next-generation sequencing (NGS) data of SARS-CoV-2. Starting from DI-tector, a bioinformatic tool for the detection of viral defective interfering genomes, here we introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. This new tool allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. As a proof of principle, we analyzed new data sets and successfully detected the nested set of sgRNAs produced with the ranking M>ORF3a>N>ORF6>ORF7a>ORF8>S>E>ORF7b. Our study also compared, for the first time for SARS-CoV-2, the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.
2021-12-28 | GSE180632 | GEO
Project description:Applying defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs
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Project description:Influenza Defective Interference Particles sequencing
| PRJNA527853 | ENA
Project description:A defective pentose phosphate pathway reduces inflammatory macrophage responses during hypercholesterolemia
| PRJNA420032 | ENA
Project description:We find that MIWI2 protein is expressed in a discrete population of multiciliated airway epithelial cells of the lung. The isolation and the next generation sequencing of the MIWI2-positive multiciliated cells revealed that they are phenotypically distinct from neighboring MIWI2-negative multiciliated cells.
2017-09-19 | GSE101806 | GEO