A novel mechanism for the inhibition of interferon regulatory factor-3-dependent gene expression by human respiratory syncytial virus NS1 protein

Junping Ren, Tianshuang Liu, Lan Pang, Kui Li, Roberto P. Garofalo, Antonella Casola, Xiaoyong Bao

Research output: Contribution to journalArticle

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Abstract

Human respiratory syncytial virus (RSV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN)-dependent signalling, as well as IFN synthesis. RSV non-structural protein NS1 plays a significant role in this inhibition; however, the mechanism(s) responsible is not fully known. The transcription factor interferon regulatory factor (IRF)-3 is essential for viralinduced IFN-β synthesis. In this study, we found that NS1 protein inhibits IRF-3-dependent gene transcription in constitutively active IRF-3 overexpressing cells, demonstrating that NS1 directly targets IRF-3. Our data also demonstrate that NS1 associates with IRF-3 and its transcriptional coactivator CBP, leading to disrupted association of IRF-3 to CBP and subsequent reduced binding of IRF-3 to the IFN-β promoter without blocking viral-induced IRF-3 phosphorylation, nuclear translocation and dimerization, thereby identifying a novel molecular mechanism by which RSV inhibits IFN-β synthesis.

Original languageEnglish (US)
Pages (from-to)2153-2159
Number of pages7
JournalJournal of General Virology
Volume92
Issue number9
DOIs
StatePublished - Sep 1 2011

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Interferon Regulatory Factor-3
Human respiratory syncytial virus
Gene Expression
Interferons
Proteins
Respiratory Syncytial Viruses
Viral Structural Proteins
Interferon Type I
Dimerization
Respiratory Tract Infections
Transcription Factors
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

A novel mechanism for the inhibition of interferon regulatory factor-3-dependent gene expression by human respiratory syncytial virus NS1 protein. / Ren, Junping; Liu, Tianshuang; Pang, Lan; Li, Kui; Garofalo, Roberto P.; Casola, Antonella; Bao, Xiaoyong.

In: Journal of General Virology, Vol. 92, No. 9, 01.09.2011, p. 2153-2159.

Research output: Contribution to journalArticle

Ren, Junping ; Liu, Tianshuang ; Pang, Lan ; Li, Kui ; Garofalo, Roberto P. ; Casola, Antonella ; Bao, Xiaoyong. / A novel mechanism for the inhibition of interferon regulatory factor-3-dependent gene expression by human respiratory syncytial virus NS1 protein. In: Journal of General Virology. 2011 ; Vol. 92, No. 9. pp. 2153-2159.
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