Molecular basis for human respiratory syncytial virus transcriptional regulator NS1 interactions with MED25

Human Respiratory Syncytial Virus (hRSV) is a prevalent pathogen posing significant risks to infants and older adults. While the roles of RSV non-structural proteins NS1 protein in modulating host immune responses remains poorly defined, its potential impact on viral pathogenicity is critical. We employed CUT&RUN of NS1, Mediator, and ATF3 in WT NS1 and mutant NS1 expressing A549 cells and bulk RNA sequencing of WT and mutant NS1-expressing A549 (GSE155151) and RSV infection in human lung air-liquid interface (ALI) cultures to elucidate the perterbations of transcriptional regulatory control induced by NS1. Coupled with our earlier work, these epigenomic and transcriptomic profiling datasets provides deeper insights into the molecular mechanisms through which RSV NS1 protein disrupts host immune functions. RNA-seq profiling of human tracheobronchialepithelial cells (hTEC) mock-infected or infected with hRSV A2 strain at MOI 3 for 72 hours. CUT&RUN sequencing of NS1, Mediator, and ATF3 in WT NS1 and mutant NS1 expressing A549 cells.