title: Mx Is Not Responsible for the Antiviral Activity of Interferon-α against Japanese Encephalitis Virus.
abstract: Mx proteins are interferon (IFN)-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV) infection is unknown. In this study, we set out to investigate the effects of Mx1 and Mx2 expression on the interferon-α (IFNα) restriction of JEV replication. To evaluate whether the inhibitory activity of IFNα on JEV is dependent on Mx1 or Mx2, we knocked down Mx1 or Mx2 with siRNA in IFNα-treated PK-15 cells and BHK-21 cells, then challenged them with JEV; the production of progeny virus was assessed by plaque assay, RT-qPCR, and Western blotting. Our results demonstrated that depletion of Mx1 or Mx2 did not affect JEV restriction imposed by IFNα, although these two proteins were knocked down 66% and 79%, respectively. Accordingly, expression of exogenous Mx1 or Mx2 did not change the inhibitory activity of IFNα to JEV. In addition, even though virus-induced membranes were damaged by Brefeldin A (BFA), overexpressing porcine Mx1 or Mx2 did not inhibit JEV proliferation. We found that BFA inhibited JEV replication, not maturation, suggesting that BFA could be developed into a novel antiviral reagent. Collectively, our findings demonstrate that IFNα inhibits JEV infection by Mx-independent pathways.
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. 2015107081@njau.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. 15150560620@163.com.
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: Wang
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai 200241, China. weijianchao@shvri.ac.cn.
authors.forename: Jian-Chao
authors.initials: JC
authors.lastname: Wei
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. xiaomin107228@126.com.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. 2014107082@njau.edu.cn.
authors.forename: Zhi-Can
authors.initials: ZC
authors.lastname: Gao
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai 200241, China. liuke@shvri.ac.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai 200241, China. zhiyongma@shvri.ac.cn.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Ma
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. puyanchennj@163.com.
authors.forename: Pu-Yan
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. zhoubin@njau.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D006224:Cricetinae; D004664:Encephalitis Virus, Japanese / Q000276:immunology* / Q000502:physiology; D007155:Immunologic Factors / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology*; D064547:Myxovirus Resistance Proteins / Q000494:pharmacology*; D013552:Swine; D019562:Viral Load; D010948:Viral Plaque Assay; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D064547:Myxovirus Resistance Proteins
keywords: Brefeldin A (BFA); Japanese encephalitis virus (JEV); Mx1; Mx2; antivirus; interferon-α (IFNα)