Newcastle Disease Virus V Protein Targets Phosphorylated STAT1 to Block IFN-I Signaling.

Xusheng Qiu, Qiang Fu, Chunchun Meng, Shengqing Yu, Yuan Zhan, Luna Dong, Cuiping Song, Yingjie Sun, Lei Tan, Shunlin Hu, Xiaoquan Wang, Xiaowen Liu, Daxin Peng, Xiufan Liu, Chan Ding

Index: PLoS ONE 11 , e0148560, (2016)

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Abstract

Newcastle disease virus (NDV) V protein is considered as an effector for IFN antagonism, however, the mechanism remains unknown. In this study, the expression of STAT1 and phospho-STAT1 in cells infected with NDV or transfected with V protein-expressing plasmids were analyzed. Our results showed that NDV V protein targets phospho-STAT1 reduction in the cells depends on the stimulation of IFN-α. In addition, a V-deficient genotype VII recombinant NDV strain rZJ1-VS was constructed using reverse genetic technique to confirm the results. The rZJ1-VS lost the ability to reduce phospho-STAT1 and induced higher expression of IFN-responsive genes in infected cells. Furthermore, treatment with an ubiquitin E1 inhibitor PYR-41 demonstrated that phospho-STAT1 reduction was caused by degradation, but not de-phosphorylation. We conclude that NDV V protein targets phospho-STAT1 degradation to block IFN-α signaling, which adds novel knowledge to the strategies used by paramyxoviruses to evade IFN.