title: The respiratory syncytial virus (RSV) nonstructural proteins mediate RSV suppression of glucocorticoid receptor transactivation.
abstract: Respiratory syncytial virus (RSV)-induced bronchiolitis in infants is not responsive to glucocorticoids. We have shown that RSV infection impairs glucocorticoid receptor (GR) function. In this study, we have investigated the mechanism by which RSV impairs GR function. We have shown that RSV repression of GR-induced transactivation is not mediated through a soluble autocrine factor. Knock-down of mitochondrial antiviral signaling protein (MAVS), but not retinoic acid-inducible gene 1 (RIG-I) or myeloid differentiation primary response gene 88 (MyD88), impairs GR-mediated gene activation even in mock-infected cells. Over-expression of the RSV nonstructural protein NS1, but not NS2, impairs glucocorticoid-induced transactivation and viruses deleted in NS1 and/or NS2 are unable to repress glucocorticoid-induction of the known GR regulated gene glucocorticoid-inducible leucine zipper (GILZ). These data suggest that the RSV nonstructural proteins mediate RSV repression of GR-induced transactivation and that inhibition of the nonstructural proteins may be a viable target for therapy against RSV-related disease.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, United States; Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, United States. Electronic address: jeanette.marketon@gmail.com.
authors.forename: Jeanette I
authors.initials: JI
authors.lastname: Webster Marketon
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, United States. Electronic address: Jacqueline.corry@nationwidechildrens.org.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Corry
authors.affiliation: Joy McCann Culverhouse Airway Disease Research Center, Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Teng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005938:Glucocorticoids; C505371:MAVS protein, human; C512343:NS2 protein, human respiratory syncytial virus; D011965:Receptors, Glucocorticoid; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: Gene regulation; Glucocorticoid; Nonstructural proteins; Respiratory syncytial virus