3 years ago

Porcine Mx1 protein inhibits classical swine fever virus replication by targeting nonstructural protein NS5B.

Yun-Na Zhang, Bin Zhou, Lin Kan, Wen-Liang Li, Xiao-Min Zhang, Jing Chen, Chun-Chun Liu, Jin-Xiu Hou, Zhi-Can Gao, Jing Zhou, Zhao-Yao Li
Mx proteins are interferon-induced GTPases that have broad antiviral activity against a wide range of RNA and DNA viruses; they belong to the dynamin superfamily of large GTPases. In this study, we confirmed the anti-CSFV activity of porcine Mx1 in vitro and showed that porcine Mx2 (poMx2), human MxA (huMxA), and mouse Mx1 (mmMx1) also have anti-CSFV activity in vitro. siRNA experiments revealed that depletion of endogenous poMx1 or poMx2 enhanced CSFV replication, suggesting that porcine Mx proteins are responsible for the antiviral activity of interferon-α (IFNα) against CSFV infection. Confocal microscopy, immunoprecipitation, glutathione S-transferase (GST) pull-down and bimolecular fluorescence complementation (BiFC) demonstrated that poMx1 associated with NS5B, the RNA-dependent RNA polymerase of CSFV. We used mutations in the poMX1 protein to elucidate the mechanism of their anti-CSFV activity and found that those that disrupted the association with NS5B, lost all anti-CSV activity. Moreover, RNA-dependent RNA polymerase (RdRp) activity assay further revealed that poMx1 undermined the RdRp activities of NS5B. Taken together, porcine Mx proteins exert their antiviral activity against CSFV by interacting with NS5B.Importance: Our previous studies have shown that porcine Mx1 (poMx1) inhibits classical swine fever virus (CSFV) replication in vitro and in vivo, but the molecular mechanism of action remains largely unknown. In this study we dissect the molecular mechanism of porcine Mx1 and Mx2 against CSFV in vitro Our results show that poMx1 associates with NS5B, the RNA-dependent RNA polymerase of CSFV, resulting in the reduction of CSFV replication. Moreover, the mutants of poMX1 further elucidate the mechanism of their anti-CSFV activities.

Publisher URL: http://doi.org/10.1128/JVI.02147-17

DOI: 10.1128/JVI.02147-17

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