title: MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction.
abstract: MicroRNAs (miRNAs) play an important role in the regulation of immune responses. Previous studies have indicated that dysregulating the miRNAs leads to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it is not clear how PRRSV regulates the expression of host miRNA, which may lead to immune escape or promote the replication of the virus. The present work suggests that PRRSV upregulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells. Furthermore, this work demonstrated that miR-373 promoted the replication of PRRSV, since miR-373 was a novel negative miRNA for the production of beta interferon (IFN-β) by targeting nuclear factor IA (NFIA), NFIB, interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, and interferon regulatory factor 1 (IRF1). We also found that both NFIA and NFIB were novel proteins for inducing the production of IFN-β, and both of them could inhibit the replication of PRRSV. In conclusion, PRRSV upregulated the expression of miR-373 by elevating the expression of Sp1 and hijacked the host miR-373 to promote the replication of PRRSV by negatively regulating the production of IFN-β.
  
  
  OBJECTIVE
  PRRSV causes one of the most economically devastating diseases of swine, and there is no effective method for controlling PRRSV. It is not clear how PRRSV inhibits the host's immune response and induces persistent infection. Previous studies have shown that PRRSV inhibited the production of type I IFN, and the treatment of type I IFN could efficiently inhibit the replication of PRRSV, so it will be helpful to design new methods of controlling PRRSV by understanding the molecular mechanism by which PRRSV modulated the production of IFN. The current work shows that miR-373, upregulated by PRRSV, promotes PRRSV replication, since miR-373 impaired the production of IFN-β by targeting NFIA, NFIB, IRAK1, IRAK4, and IRF1, and both NFIA and NFIB were antiviral proteins to PRRSV. In conclusion, this paper revealed a novel mechanism of PRRSV that impaired the production of type I IFN by upregulating miR-373 expression in MARC-145 cells.
authors.affiliation: College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.|Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Henan Normal University, Xinxiang, China shixibao@aliyun.com zhanggaiping2003@163.com.|Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China.
authors.forename: Xibao
authors.initials: X
authors.lastname: Shi
authors.affiliation: College of Life Sciences, Henan Normal University, Xinxiang, China.
authors.forename: Xiaozhuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, Zhengzhou University, Zhengzhou, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China.
authors.forename: Ruiguang
authors.initials: R
authors.lastname: Deng
authors.affiliation: College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China shixibao@aliyun.com zhanggaiping2003@163.com.|Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China.|College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.|Department of Bioengineering, Zhengzhou University, Zhengzhou, China.|Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Gai-Ping
authors.initials: GP
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013552:Swine; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D035683:MicroRNAs; D051839:NFI Transcription Factors; D016329:Sp1 Transcription Factor; D014764:Viral Proteins
keywords: IFN-β; NFIA; NFIB; PRRSV; Sp1; miR-373