Details

Autor(en) / Beteiligte

• Pei, Jingjing
• Beri, Nina R.
• Zou, Angela J.
• Hubel, Philipp
• Dorando, Hannah K.
• Bergant, Valter
• Andrews, Rebecca D.
• Pan, Jiehong
• Andrews, Jared M.
• Sheehan, Kathleen C.F.
• Pichlmair, Andreas
• Amarasinghe, Gaya K.
• Brody, Steven L.
• Payton, Jacqueline E.
• Leung, Daisy W.

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2021-10, Vol.37 (2), p.109803-109803, Article 109803

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV. [Display omitted] •NS1 partitions into the nucleus upon RSV infection•NS1 coimmunoprecipitates with chromatin-associated proteins•NS1 binds regulatory elements of differentially expressed genes in RSV infection•NS1 modulates host gene transcription Pei et al. show that NS1 is present in the nucleus in primary airway epithelial, MDDCs, and A549 cells upon RSV infection. This study finds that NS1 functions as an immune antagonist by binding chromatin at the promoters and enhancers of immune response genes and modulating host gene transcription.