Respiratory Syncytial Virus Nonstructural Protein 1 Blocks Glucocorticoid Receptor Nuclear Translocation by Targeting IPO13 and May Account for Glucocorticoid Insensitivity.
J Infect Dis
; 217(1): 35-46, 2017 12 27.
Article
em En
| MEDLINE
| ID: mdl-28968829
ABSTRACT
Despite 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus Sinciciais Respiratórios
/
Receptores de Glucocorticoides
/
Proteínas não Estruturais Virais
/
Infecções por Vírus Respiratório Sincicial
/
Carioferinas
/
Interações Hospedeiro-Patógeno
/
Glucocorticoides
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article