PMID- 24418538 OWN - NLM STAT- MEDLINE DCOM- 20140407 LR - 20231213 IS - 1096-0341 (Electronic) IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 449 DP - 2014 Jan 20 TI - The respiratory syncytial virus (RSV) nonstructural proteins mediate RSV suppression of glucocorticoid receptor transactivation. PG - 62-9 LID - S0042-6822(13)00627-2 [pii] LID - 10.1016/j.virol.2013.11.014 [doi] AB - 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. CI - (c) 2013 Published by Elsevier Inc. FAU - Webster Marketon, Jeanette I AU - Webster Marketon JI AD - 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. FAU - Corry, Jacqueline AU - Corry J AD - 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. FAU - Teng, Michael N AU - Teng MN AD - 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. LA - eng GR - R01 AI081977/AI/NIAID NIH HHS/United States GR - R01AI081977/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131126 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Glucocorticoids) RN - 0 (MAVS protein, human) RN - 0 (NS2 protein, human respiratory syncytial virus) RN - 0 (Receptors, Glucocorticoid) RN - 0 (Receptors, Immunologic) RN - 0 (Viral Nonstructural Proteins) RN - EC 3.6.1.- (RIGI protein, human) RN - EC 3.6.4.13 (DEAD Box Protein 58) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics/metabolism MH - DEAD Box Protein 58 MH - DEAD-box RNA Helicases/genetics/metabolism MH - Down-Regulation MH - Glucocorticoids/metabolism MH - Humans MH - Receptors, Glucocorticoid/genetics/*metabolism MH - Receptors, Immunologic MH - Respiratory Syncytial Virus Infections/genetics/*metabolism/virology MH - Respiratory Syncytial Virus, Human/genetics/*metabolism MH - *Transcriptional Activation MH - Viral Nonstructural Proteins/genetics/*metabolism PMC - PMC3904736 MID - NIHMS544859 OTO - NOTNLM OT - Gene regulation OT - Glucocorticoid OT - Nonstructural proteins OT - Respiratory syncytial virus EDAT- 2014/01/15 06:00 MHDA- 2014/04/08 06:00 PMCR- 2015/01/20 CRDT- 2014/01/15 06:00 PHST- 2013/06/06 00:00 [received] PHST- 2013/07/12 00:00 [revised] PHST- 2013/11/06 00:00 [accepted] PHST- 2014/01/15 06:00 [entrez] PHST- 2014/01/15 06:00 [pubmed] PHST- 2014/04/08 06:00 [medline] PHST- 2015/01/20 00:00 [pmc-release] AID - S0042-6822(13)00627-2 [pii] AID - 10.1016/j.virol.2013.11.014 [doi] PST - ppublish SO - Virology. 2014 Jan 20;449:62-9. doi: 10.1016/j.virol.2013.11.014. Epub 2013 Nov 26.