title: MicroRNA miR-24-3p promotes porcine reproductive and respiratory syndrome virus replication through suppression of heme oxygenase-1 expression.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important viruses affecting the swine industry worldwide. Our previous research showed that PRRSV downregulates the expression of heme oxygenase-1 (HO-1), a pivotal cytoprotective enzyme, postinfection and that overexpression of HO-1 inhibits PRRSV replication. MicroRNAs regulate gene expression at the posttranscriptional level and have recently been demonstrated to play vital roles in pathogen-host interactions. The present study sought to determine whether microRNAs modulate HO-1 expression and, by doing so, regulate PRRSV replication. Using bioinformatic prediction and experimental verification, we demonstrate that HO-1 expression is regulated by miR-24-3p. A direct interaction between miR-24-3p and HO-1 mRNA was confirmed using a number of approaches. Overexpression of miR-24-3p significantly decreased HO-1 mRNA and protein levels. PRRSV infection induced miR-24-3p expression to facilitate viral replication. The suppressive effect of HO-1 induction by protoporphyrin IX cobalt chloride (CoPP; a classical inducer of HO-1 expression) on PRRSV replication in MARC-145 cells and primary porcine alveolar macrophages could also be reversed by overexpression of miR-24-3p. Collectively, these results suggested that miR-24-3p promotes PRRSV replication through suppression of HO-1 expression, which not only provides new insights into virus-host interactions during PRRSV infection but also suggests potential new antiviral strategies against PRRSV infection.
  
  
  OBJECTIVE
  MicroRNAs (miRNAs) play vital roles in viral infections by regulating the expression of viral or host genes at the posttranscriptional level. Heme oxygenase-1 (HO-1), a pivotal cytoprotective enzyme, has antiviral activity for a number of viruses, such as Ebola virus, hepatitis C virus, human immunodeficiency virus, and our focus, PRRSV, which causes great economic losses each year in the swine industry worldwide. Here, we show that PRRSV infection induces host miRNA miR-24-3p expression and that miR-24-3p regulates HO-1 expression through both mRNA degradation and translation repression. Suppression of HO-1 expression by miR-24-3p facilitates PRRSV replication. This work lends credibility to the hypothesis that an arterivirus can manipulate cellular miRNAs to enhance virus replication by regulating antiviral responses following viral infection. Therefore, our findings provide new insights into the pathogenesis of PRRSV.
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Shuqi
authors: S
authors: Xiao
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Xue
authors: X
authors: Wang
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Huaibao
authors: H
authors: Ni
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Na
authors: N
authors: Li
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Angke
authors: A
authors: Zhang
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Hongliang
authors: H
authors: Liu
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Fengxing
authors: F
authors: Pu
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Lele
authors: L
authors: Xu
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Jiming
authors: J
authors: Gao
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Qin
authors: Q
authors: Zhao
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Yang
authors: Y
authors: Mu
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Chengbao
authors: C
authors: Wang
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Yani
authors: Y
authors: Sun
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Taofeng
authors: T
authors: Du
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
authors: Xingang
authors: X
authors: Xu
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China.
authors: Gaiping
authors: G
authors: Zhang
authors: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors: Julian A
authors: JA
authors: Hiscox
authors: Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Ian G
authors: IG
authors: Goodfellow
authors: College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China zhouem@nwsuaf.edu.cn.
authors: En-Min
authors: EM
authors: Zhou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D047468:Immunoprecipitation; D008156:Luciferases; D008253:Macaca mulatta; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D034421:Sus scrofa; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D008156:Luciferases; D051547:Heme Oxygenase-1
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