Circadian Rhythm in Coronavirus Pneumonia Severity

The goal of this experiment is to examine how circadian rhythms affect coronavirus pneumonia severity. To this end, we infected mice at different times of day with mouse hepatitis virus-1 (MHV-1), which is a beta-coronavirus native to rodents that produces similar histological features as SARS, MERS, and COVID-19. Bulk RNAseq was used to generate a list of differentially expressed genes (DEGs) based on the circadian time of MHV-1 exposure. mice The cells were synchronized with 100nM dexmethosone to produce coherent circadian gene expression patterns in the cultures. Cells were then longitudinally harvested every 4 hours for 48 hours starting 12 hours after dexamethasone treatment. To obtain basic spatial information, we also analyzed lung parenchyma and BAL cells separately, representing the lung parenchyma and luminal airspace compartment that is largely composed of AMs and other luminal macrophages. In both the lung parenchyma and BAL, the number of time-sensitive DEGs also peaked at 2 DPI. DEGs overexpressed with ZT6 infection proved functionally enriched for inflammatory pathways, interferon signaling, and circadian rhythms.