title: Human respiratory syncytial virus non-structural   protein NS1 modifies miR-24 expression via   transforming growth factor-β.
abstract: Human respiratory syncytial virus (RSV) is a major health challenge in the young and elderly owing to the lack of a safe and effective vaccine and proven antiviral drugs. Understanding the mechanisms by which viral genes and proteins modulate the host response to infection is critical for identifying novel disease intervention strategies. In this study, the RSV non-structural protein NS1 was shown to suppress miR-24 expression during infection. Lack of NS1 was linked to increased expression of miR-24, whilst NS1 overexpression suppressed miR-24 expression. NS1 was found to induce Kruppel-like factor 6 (KLF6), a transcription factor that positively regulates the transforming growth factor (TGF)-b pathway to induce cell cycle arrest. Silencing of KLF6 led to increased miR-24 expression via downregulation of TGF-β. Treatment with exogenous TGF-β suppressed miR-24 expression and induced KLF6. Confocal microscopy showed co-localization of KLF6 and RSV NS1. These findings indicated that RSV NS1 interacts with KLF6 and modulates miR-24 expression and TGF-β, which facilitates RSV replication.
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Bakre
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Weining
authors.initials: W
authors.lastname: Wu
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Hiscox
authors.affiliation: School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Spann
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Teng
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D054884:Host-Pathogen Interactions; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D017361:Viral Nonstructural Proteins