BMAL1 modulates respiratory syncytial virus-induced inflammation through p38 mitogen-activated protein kinase...

Respiratory syncytial virus (RSV) is the most common pathogen of acute lower respiratory tract infection in children under 5 years old. Here, we aims to investigate the role of the central clock gene BMAL1 in RSV infection.

The rhythmic oscillation of clock genes, pro-inflammatory factors, viral loads and p-p38/p38 in the lung of mice were observed. BMAL1 knockdown mice, Beas-2B cells and jet-lagged mice were infected with RSV. The virus copy numbers, expression of inflammatory factors and clock genes, and pathological inflammatory infiltration of the lung were measured. Transcriptomic analysis was performed to find the possible pathway.

The expression of clock genes in the lungs of mice exhibited circadian rhythmicity. The rhythmic oscillation amplitude and trend of clock genes, inflammatory factors, DUSP1, and p-p38/p38 in the lung of RSV infected mice were altered. BMAL1-knockdown and jet-lagged mice showed exacerbated RSV infection and RSV-induced inflammation in the lung. Analysis of transcriptomes showed that BMAL1 regulated RSV-induced inflammation through the p38 MAPK axis. Regulation of RSV infection by BMAL1 was also confirmed in Beas-2B cells.

RSV infection affects the expression of clock genes in Beas-2B cells and lungs of mice, and alters the rhythmic oscillation patterns of pro-inflammatory factors, DUSP1 and p-p38/p38 in the lungs. BMAL1 disruption is identified as a potential pathological factor of RSV-associated inflammation. p38 MAPK pathway is involved in the regulation of RSV infection and RSV-induced inflammation by BMAL1.