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Article: Respiratory Syncytial Virus Nonstructural Protein 1 Blocks Glucocorticoid Receptor Nuclear Translocation by Targeting IPO13 and May Account for Glucocorticoid Insensitivity

TitleRespiratory Syncytial Virus Nonstructural Protein 1 Blocks Glucocorticoid Receptor Nuclear Translocation by Targeting IPO13 and May Account for Glucocorticoid Insensitivity
Authors
KeywordsRSV
glucocorticoid
GR
nuclear translocation
IPO13
Issue Date2018
PublisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org
Citation
The Journal of Infectious Diseases, 2018, v. 217 n. 1, p. 35-46 How to Cite?
AbstractDespite their powerful antiinflammatory effect, glucocorticoids have shown no significant clinical benefit in respiratory syncytial virus (RSV)–induced bronchiolitis, the reason for which remains unclear. Upon glucocorticoid binding, the cytoplasmic glucocorticoid receptor (GR) translocates to the nucleus with the help of importin 13 (IPO13). Here, we report that RSV infection reduced GR nuclear translocation in nasopharyngeal aspirates from RSV-infected infants, lungs of infected mice, and A549 cells, which coincided with decreased IPO13 expression. This led to repression of GR-induced antiinflammatory genes, such that dexamethasone failed to suppress airway inflammation and airway hyperresponsiveness in the infected mice. The anti-GR effect of RSV was mediated by viral nonstructural protein 1 , which likely functioned by competing with IPO13 for GR binding. Our findings provide a mechanism for the ineffectiveness of glucocorticoids in RSV-related disease and highlight the potential to target the IPO13-GR axis as a treatment for multiple glucocorticoid-related diseases.
DescriptionLink to Free access
Persistent Identifierhttp://hdl.handle.net/10722/279194
ISSN
2019 Impact Factor: 5.022
2015 SCImago Journal Rankings: 4.000

 

DC FieldValueLanguage
dc.contributor.authorXie, J-
dc.contributor.authorLong, X-
dc.contributor.authorGao, L-
dc.contributor.authorChen, S-
dc.contributor.authorZhao, K-
dc.contributor.authorLi, W-
dc.contributor.authorZhao, N-
dc.contributor.authorZang, N-
dc.contributor.authorDeng, Y-
dc.contributor.authorRen, L-
dc.contributor.authorWang, L-
dc.contributor.authorLuo, Z-
dc.contributor.authorTu, W-
dc.contributor.authorZhao, X-
dc.contributor.authorFu, Z-
dc.contributor.authorXie, X-
dc.contributor.authorLiu, E-
dc.date.accessioned2019-10-21T02:21:20Z-
dc.date.available2019-10-21T02:21:20Z-
dc.date.issued2018-
dc.identifier.citationThe Journal of Infectious Diseases, 2018, v. 217 n. 1, p. 35-46-
dc.identifier.issn0022-1899-
dc.identifier.urihttp://hdl.handle.net/10722/279194-
dc.descriptionLink to Free access-
dc.description.abstractDespite their powerful antiinflammatory effect, glucocorticoids have shown no significant clinical benefit in respiratory syncytial virus (RSV)–induced bronchiolitis, the reason for which remains unclear. Upon glucocorticoid binding, the cytoplasmic glucocorticoid receptor (GR) translocates to the nucleus with the help of importin 13 (IPO13). Here, we report that RSV infection reduced GR nuclear translocation in nasopharyngeal aspirates from RSV-infected infants, lungs of infected mice, and A549 cells, which coincided with decreased IPO13 expression. This led to repression of GR-induced antiinflammatory genes, such that dexamethasone failed to suppress airway inflammation and airway hyperresponsiveness in the infected mice. The anti-GR effect of RSV was mediated by viral nonstructural protein 1 , which likely functioned by competing with IPO13 for GR binding. Our findings provide a mechanism for the ineffectiveness of glucocorticoids in RSV-related disease and highlight the potential to target the IPO13-GR axis as a treatment for multiple glucocorticoid-related diseases.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org-
dc.relation.ispartofThe Journal of Infectious Diseases-
dc.rightsPre-print: Journal Title] ©: [year] [owner as specified on the article] Published by Oxford University Press [on behalf of xxxxxx]. All rights reserved. Pre-print (Once an article is published, preprint notice should be amended to): This is an electronic version of an article published in [include the complete citation information for the final version of the Article as published in the print edition of the Journal.] Post-print: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [insert journal title] following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: xxxxxxx [insert URL that the author will receive upon publication here].-
dc.subjectRSV-
dc.subjectglucocorticoid-
dc.subjectGR-
dc.subjectnuclear translocation-
dc.subjectIPO13-
dc.titleRespiratory Syncytial Virus Nonstructural Protein 1 Blocks Glucocorticoid Receptor Nuclear Translocation by Targeting IPO13 and May Account for Glucocorticoid Insensitivity-
dc.typeArticle-
dc.identifier.emailTu, W: wwtu@hku.hk-
dc.identifier.authorityTu, W=rp00416-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/infdis/jix445-
dc.identifier.pmid28968829-
dc.identifier.scopuseid_2-s2.0-85044079417-
dc.identifier.hkuros307780-
dc.identifier.volume217-
dc.identifier.issue1-
dc.identifier.spage35-
dc.identifier.epage46-
dc.publisher.placeUnited States-

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