Pluto Bioinformatics

GSE140226 (mouse): Dexamethasone inhibits respiratory syncytial virus-driven mucus production while increasing viral replication without altering antiviral interferon signaling

Bulk RNA sequencing

Purpose: To understand how dexamethasone has beneficial effects on reducing mucus production but inhibits viral defense mechanisms; Methods: RSV-infected mouse lungs and various cell lines, plus and minus dexamethason, were examined by RNAseq, and pathway analysis of differentially-expressed genes were compared; Results: Using RNA-seq we identified a subset of cytokines that were induced by RSV and repressed by dexamethasone. Interestingly, while RSV induced interferons (IFNs) and IFN stimulated genes (ISGs), dexamethasone treatment did not affect the expression of these genes or antiviral IFN signaling pathways as has been observed with glucocorticoid treatment of other respiratory viruses [13]. Using an unbiased approach, we found that certain RSV-driven gene expression networks and genes were specifically modulated by dexamethasone treatment. Importantly, dexamethasone also reduced RSV clearance in vivo, which correlated with a reduction in specific immune response markers.; Conclusion: Our results support the possibility that the beneficial anti-inflammatory effects of dexamethasone treatment are counterbalanced by the increased viral load in patients, accounting for the lack of clinical benefit derived from treatment during RSV infection. SOURCE: John,R,Walker (jwalker@gnf.org) - Genetics Core Genomics Institute of the Novartis Research Foundation