Abstract
Abstract Human respiratory syncytial virus (RSV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN)-dependent signaling, as well as IFN synthesis. RSV nonstructural protein NS1 plays a significant role in this inhibition, however the mechanism(s) responsible are not fully known. The transcription factor interferon regulatory factor (IRF)-3 is essential for viral-induced 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. NS1 associates with IRF-3 and inhibits IFN-β transcription by blocking IRF-3 binding to the IFN-β promoter, without affecting viral-induced IRF-3 phosphorylation and nuclear translocation, thereby identifying a novel molecular mechanism by which RSV inhibits IFN-β synthesis.
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