MicroRNA miR-24-3p Promotes Porcine Reproductive and Respiratory Syndrome Virus Replication through Suppression of Heme Oxygenase-1 Expression

被引:87
作者
Xiao, Shuqi [1 ,2 ]
Wang, Xue [1 ,2 ]
Ni, Huaibao [1 ,2 ]
Li, Na [1 ,2 ]
Zhang, Angke [1 ,2 ]
Liu, Hongliang [1 ,2 ]
Pu, Fengxing [1 ,2 ]
Xu, Lele [1 ,2 ]
Gao, Jiming [1 ,2 ]
Zhao, Qin [1 ,2 ]
Mu, Yang [1 ,2 ]
Wang, Chengbao [1 ,2 ]
Sun, Yani [1 ,2 ]
Du, Taofeng [1 ,2 ]
Xu, Xingang [1 ,2 ]
Zhang, Gaiping [1 ,3 ]
Hiscox, Julian A. [4 ]
Goodfellow, Ian G. [5 ]
Zhou, En-Min [1 ,2 ]
机构
[1] Northwest A&F Univ, Coll Vet Med, Yangling, Shaanxi, Peoples R China
[2] Minist Agr, Expt Stn Vet Pharmacol & Vet Biotechnol, Beijing, Shaanxi, Peoples R China
[3] Henan Agr Univ, Coll Anim Sci & Vet Med, Zhengzhou, Henan, Peoples R China
[4] Univ Liverpool, Dept Infect Biol, Inst Infect & Global Hlth, Liverpool L69 3BX, Merseyside, England
[5] Univ Cambridge, Addenbrookes Hosp, Dept Pathol, Div Virol, Cambridge CB2 2QQ, England
基金
英国惠康基金; 中国国家自然科学基金;
关键词
ANTIBODY-DEPENDENT ENHANCEMENT; PRRSV INFECTION; MARC-145; CELLS; OXIDANT INJURY; MACROPHAGES; INHIBITION; MECHANISM; CHINA; TRANSCRIPTION; PATHOGENESIS;
D O I
10.1128/JVI.02810-14
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 pathogenhost 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 miR24-3p 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. IMPORTANCE 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.
引用
收藏
页码:4494 / 4503
页数:10
相关论文
共 51 条
[1]   Antibody-dependent enhancement of PRRSV infection down-modulates TNF-α and IFN-β transcription in macrophages [J].
Bao, Dengke ;
Wang, Rui ;
Qiao, Songlin ;
Wan, Bo ;
Wang, Yinbiao ;
Liu, Mingyang ;
Shi, Xibao ;
Guo, Juiqing ;
Zhang, Gaiping .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2013, 156 (1-2) :128-134
[2]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   The microRNA.org resource: targets and expression [J].
Betel, Doron ;
Wilson, Manda ;
Gabow, Aaron ;
Marks, Debora S. ;
Sander, Chris .
NUCLEIC ACIDS RESEARCH, 2008, 36 :D149-D153
[5]   Genomic Evolution of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Isolates Revealed by Deep Sequencing [J].
Brar, Manreetpal Singh ;
Shi, Mang ;
Hui, Raymond Kin-Hi ;
Leung, Frederick Chi-Ching .
PLOS ONE, 2014, 9 (04)
[6]   Integrated analysis of microRNA and mRNA expression and association with HIF binding reveals the complexity of microRNA expression regulation under hypoxia [J].
Camps, Carme ;
Saini, Harpreet K. ;
Mole, David R. ;
Choudhry, Hani ;
Reczko, Martin ;
Guerra-Assuncao, Jose Afonso ;
Tian, Ya-Min ;
Buffa, Francesca M. ;
Harris, Adrian L. ;
Hatzigeorgiou, Artemis G. ;
Enright, Anton J. ;
Ragoussis, Jiannis .
MOLECULAR CANCER, 2014, 13
[7]   Role of haem oxygenase-1 in microbial host defence [J].
Chung, Su Wol ;
Hall, Sean R. ;
Perrella, Mark A. .
CELLULAR MICROBIOLOGY, 2009, 11 (02) :199-207
[8]   Hemin activation ameliorates HIV-1 infection via heme oxygenase-1 induction [J].
Devadas, Krishnakumar ;
Dhawan, Subhash .
JOURNAL OF IMMUNOLOGY, 2006, 176 (07) :4252-4257
[9]   Regulation of mRNA Translation and Stability by microRNAs [J].
Fabian, Marc Robert ;
Sonenberg, Nahum ;
Filipowicz, Witold .
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 79, 2010, 79 :351-379
[10]   MicroRNA 181 Suppresses Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection by Targeting PRRSV Receptor CD163 [J].
Gao, Li ;
Guo, Xue-kun ;
Wang, Lianghai ;
Zhang, Qiong ;
Li, Ning ;
Chen, Xin-xin ;
Wang, Yongqiang ;
Feng, Wen-hai .
JOURNAL OF VIROLOGY, 2013, 87 (15) :8808-8812