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Yang L, Xu J, Guo L, Guo T, Zhang L, Feng L, Chen H, Wang Y. Porcine epidemic diarrhea virus-induced epidermal growth factor receptor activation impairs the antiviral activity of type I interferon. J Virol. 2018 Jan 31

发布日期:2018-02-12 17:04  浏览次数:

Porcine epidemic diarrhea virus-induced epidermal growth factor receptor activation impairs the antiviral activity of type I interferon.
Yang L, Xu J, Guo L, Guo T, Zhang L, Feng L, Chen H, Wang Y.
J Virol. 2018 Jan 31. pii: JVI.02095-17. doi: 10.1128/JVI.02095-17
Abstract
Porcine epidemic diarrhea virus (PEDV) causes acute and devastating enteric disease in suckling piglets and results in huge economic losses in pig industry worldwide. To establish productive infection, viruses must first circumvent the host innate immune response. In this study, we found that PEDV infection stimulated epidermal growth factor receptor (EGFR) activation, which has been linked to not only anticancer therapeutics but also antiviral signaling. Therefore, we determined whether EGFR activation affected PEDV infection by using activator or overexpression assay. The data showed that EGFR activation enhanced virus replication in both cases. We also found that specific inhibition of EGFR by either inhibitors or siRNA led to the decrease of virus yields. Further analysis revealed that inhibition of EGFR displayed an augmentation of type I interferon genes. We next observed that EGFR downstream cascade STAT3 was also activated upon PEDV infection. Similar to the case of EGFR, specific inhibition of STAT3 by either inhibitor or siRNA increased the antiviral activity of interferon and resulted in the decreased PEDV RNA levels, and vice versa. Data with STAT3 depletion in combination with EGFR activation suggest that the attenuation of antiviral activity by EGFR activation requires the activation of STAT3 signaling pathway. Taken together, these data demonstrate that PEDV-induced EGFR activation serves as a negative regulator of type I interferon response and provides a novel therapeutic target for virus infection.IMPORTANCE EGFR is a transmembrane tyrosine receptor that mediates various cellular events, as well as several types of human cancers. In this study, we investigated for the first time the role of EGFR on PEDV infection. We observed that PEDV infection induced EGFR activation. The role of EGFR activation is to impair the antiviral activity of type I interferon, which requires the involvement of EGFR downstream signaling cascade STAT3. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response, which might serve as a therapeutic target against virus infection.
 
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