Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription

• DOI: 10.1016/j.celrep.2021.109803
• Publication Date: 2021-10-13T14:14:42Z
• Authors: Jingjing Pei; Nina R. Beri; Angela J. Zou; Philipp Hubel; Hannah K. Dorando; Valter Bergant; Rebecca D. Andrews; Jiehong Pan; Jared M. Andrews; Kathleen C.F. She...; Andreas Pichlmair; Gaya K. Amarasinghe; Steven L. Brody; Jacqueline E. Payton; Daisy W. Leung
• Keywords: Chromatin immunoprecipitation; Mononegavirales; Transcription

Human respiratory syncytial virus (RSV) is a common cause of lower tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 known cytosolic immune antagonist, but how modulates host responses remains poorly defined. Here, we observe partitioning into nucleus RSV-infected cells, including human airway epithelium. Nuclear coimmunoprecipitates with Mediator complex chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment that overlaps transcription factor binding within promoters enhancers differentially expressed genes during infection. Mutation C-terminal helix reduces impact on gene expression. These data suggest nuclear alters to infection by at regulatory elements response modulating transcription. Our study identifies another layer regulation virally encoded proteins shapes impacts immunity RSV.