PMID- 27881653 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20220311 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 91 IP - 3 DP - 2017 Feb 1 TI - MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction. LID - 10.1128/JVI.01311-16 [doi] LID - e01311-16 AB - 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-beta) 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-beta, 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-beta. IMPORTANCE: 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-beta 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. CI - Copyright (c) 2017 American Society for Microbiology. FAU - Chen, Jing AU - Chen J AD - College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China. AD - Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China. FAU - Shi, Xibao AU - Shi X AD - College of Life Sciences, Henan Normal University, Xinxiang, China shixibao@aliyun.com zhanggaiping2003@163.com. AD - Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China. FAU - Zhang, Xiaozhuan AU - Zhang X AD - College of Life Sciences, Henan Normal University, Xinxiang, China. FAU - Wang, Aiping AU - Wang A AD - Department of Bioengineering, Zhengzhou University, Zhengzhou, China. FAU - Wang, Li AU - Wang L AD - Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China. FAU - Yang, Yanyan AU - Yang Y AD - Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China. FAU - Deng, Ruiguang AU - Deng R AD - Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China. FAU - Zhang, Gai-Ping AU - Zhang GP AD - College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China shixibao@aliyun.com zhanggaiping2003@163.com. AD - Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, China. AD - College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, China. AD - Department of Bioengineering, Zhengzhou University, Zhengzhou, China. AD - Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China. LA - eng PT - Journal Article DEP - 20170118 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Interferon Type I) RN - 0 (MicroRNAs) RN - 0 (NFI Transcription Factors) RN - 0 (Sp1 Transcription Factor) RN - 0 (Viral Proteins) SB - IM MH - Animals MH - Cell Line MH - Gene Expression Regulation MH - Interferon Type I/biosynthesis/*genetics MH - MicroRNAs/*genetics MH - NFI Transcription Factors/genetics/metabolism MH - Porcine Reproductive and Respiratory Syndrome/*genetics/metabolism/*virology MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Sp1 Transcription Factor/metabolism MH - Swine MH - Viral Proteins/metabolism MH - *Virus Replication PMC - PMC5244336 OTO - NOTNLM OT - IFN-beta OT - NFIA OT - NFIB OT - PRRSV OT - Sp1 OT - miR-373 EDAT- 2016/11/25 06:00 MHDA- 2017/05/16 06:00 PMCR- 2017/07/18 CRDT- 2016/11/25 06:00 PHST- 2016/07/07 00:00 [received] PHST- 2016/11/18 00:00 [accepted] PHST- 2016/11/25 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/11/25 06:00 [entrez] PHST- 2017/07/18 00:00 [pmc-release] AID - JVI.01311-16 [pii] AID - 01311-16 [pii] AID - 10.1128/JVI.01311-16 [doi] PST - epublish SO - J Virol. 2017 Jan 18;91(3):e01311-16. doi: 10.1128/JVI.01311-16. Print 2017 Feb 1.