{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:02:48Z","timestamp":1788447768083,"version":"build-2803163510"},"reference-count":87,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"national institutes of health NIAID and NCATS","award":["NIAID 2P01AI062885, NCATS UL1TR00237"],"award-info":[{"award-number":["NIAID 2P01AI062885, NCATS UL1TR00237"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Respiratory syncytial virus infection is responsible for seasonal upper and lower respiratory tract infections worldwide, causing substantial morbidity. Self-inoculation of the virus into the nasopharynx results in epithelial replication and distal spread into the lower respiratory tract. Here, respiratory syncytial virus (RSV) activates sentinel cells important in the host inflammatory response, resulting in epithelial-derived cytokine and interferon (IFN) expression resulting in neutrophilia, whose intensity is associated with disease severity. I will synthesize key findings describing how RSV replication activates intracellular NF\u03baB and IRF signaling cascades controlling the innate immune response (IIR). Recent studies have implicated a central role for Scg1a1+ expressing progenitor cells in IIR, a cell type uniquely primed to induce neutrophilic-, T helper 2 (Th2)-polarizing-, and fibrogenic cytokines that play distinct roles in disease pathogenesis. Molecular studies have linked the positive transcriptional elongation factor-b (P-TEFb), a pleiotrophic chromatin remodeling complex in immediate-early IIR gene expression. Through intrinsic kinase activity of cyclin dependent kinase (CDK) 9 and atypical histone acetyl transferase activity of bromodomain containing protein 4 (BRD4), P-TEFb mediates transcriptional elongation of IIR genes. Unbiased proteomic studies show that the CDK9\u2022BRD4 complex is dynamically reconfigured by the innate response and targets TGF\u03b2-dependent fibrogenic gene networks. Chronic activation of CDK9\u2022BRD4 mediates chromatin remodeling fibrogenic gene networks that cause epithelial mesenchymal transition (EMT). Mesenchymal transitioned epithelial cells elaborate TGF\u03b2 and IL6 that function in a paracrine manner to expand the population of subepithelial myofibroblasts. These findings may account for the long-term reduction in pulmonary function in children with severe lower respiratory tract infection (LRTI). Modifying chromatin remodeling properties of the CDK9\u2022BRD4 coactivators may provide a mechanism for reducing post-infectious airway remodeling that are a consequence of severe RSV LRTIs.<\/jats:p>","DOI":"10.3390\/v12040472","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T02:10:52Z","timestamp":1587607852000},"page":"472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["RSV Reprograms the CDK9\u2022BRD4 Chromatin Remodeling Complex to Couple Innate Inflammation to Airway Remodeling"],"prefix":"10.3390","volume":"12","author":[{"given":"Allan R.","family":"Brasier","sequence":"first","affiliation":[{"name":"Institute for Clinical and Translational Research; University of Wisconsin-Madison School of Medicine and Public Health; Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,22]]},"reference":[{"key":"ref_1","unstructured":"(2019). 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