Human metapneumovirus inhibits the IL-6-induced JAK/STAT3 signalling cascade in airway epithelium.
J Gen Virol
; 95(Pt 1): 26-37, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24114793
ABSTRACT
The host cytokine IL-6 plays an important role in host defence and prevention of lung injury from various pathogens, making IL-6 an important mediator in the host's susceptibility to respiratory infections. The cellular response to IL-6 is mediated through a Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signal transduction pathway. Human metapneumovirus (hMPV) is an important causative agent of viral respiratory infections known to inhibit the IFN-mediated activation of STAT1. However, little is known about the interactions between this virus and other STAT signalling cascades. Herein, we showed that hMPV can attenuate the IL-6-mediated JAK/STAT3 signalling cascade in lung epithelial cells. HMPV inhibited a key event in this pathway by impeding the phosphorylation and nuclear translocation of STAT3 in A549 cells and in primary normal human bronchial epithelial cells. Further studies established that hMPV interrupted the IL-6-induced JAK/STAT pathway early in the signal transduction pathway by blocking the phosphorylation of JAK2. By antagonizing the IL-6-mediated JAK/STAT3 pathway, hMPV perturbed the expression of IL-6-inducible genes important for apoptosis, cell differentiation and growth. Infection with hMPV also differentially regulated the effects of IL-6 on apoptosis. Thus, hMPV regulation of these genes could usurp the protective roles of IL-6, and these data provide insight into an important element of viral pathogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Interleucina-6
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Infecções por Paramyxoviridae
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Metapneumovirus
/
Células Epiteliais
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Fator de Transcrição STAT3
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Janus Quinase 2
/
Pulmão
Limite:
Humans
Idioma:
En
Revista:
J Gen Virol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos