Infection with street strain rabies virus induces modulation of the microRNA profile of the mouse brain

Virology Journal

Xianzhu Xia¹  Songtao Yang¹  Chuan Qin²  Geng Huang¹  Yuwei Gao¹  Chengyu Wang¹  Na Feng¹  Tao Xu⁴  Tiecheng Wang¹  Hualei Wang¹  Hao Feng³  Kun Zhang¹  Lili Zhao³  Pingsen Zhao¹ 

[1] Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, 130122, China;Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China;College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, China;Medical College of Soochow University, Suzhou, 215123, China

关键词: Functional enrichment;    Target prediction;    Gene profiling;    MicroRNA profiling;    Brain infection;    Street strain rabies virus;   

Others  :  1154166
DOI  :  10.1186/1743-422X-9-159

 received in 2011-06-03, accepted in 2012-07-23,  发布年份 2012

【 摘 要 】

Background

Rabies virus (RABV) causes a fatal infection of the central nervous systems (CNS) of warm-blooded animals. Once the clinical symptoms develop, rabies is almost invariably fatal. The mechanism of RABV pathogenesis remains poorly understood. Recent studies have shown that microRNA (miRNA) plays an important role in the pathogenesis of viral infections. Our recent findings have revealed that infection with laboratory-fixed rabies virus strain can induce modulation of the microRNA profile of mouse brains. However, no previous report has evaluated the miRNA expression profile of mouse brains infected with RABV street strain.

Results

The results of microarray analysis show that miRNA expression becomes modulated in the brains of mice infected with street RABV. Quantitative real-time PCR assay of the differentially expressed miRNAs confirmed the results of microarray assay. Functional analysis showed the differentially expressed miRNAs to be involved in many immune-related signaling pathways, such as the Jak-STAT signaling pathway, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and Fc gamma R-mediated phagocytosis. The predicted expression levels of the target genes of these modulated miRNAs were found to be correlated with gene expression as measured by DNA microarray and qRT-PCR.

Conclusion

RABV causes significant changes in the miRNA expression profiles of infected mouse brains. Predicted target genes of the differentially expression miRNAs are associated with host immune response, which may provide important information for investigation of RABV pathogenesis and therapeutic method.

【 授权许可】

   
2012 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

Figure 2 .

Figure 3.

Figure 4 .

【 参考文献 】

• [1]Ray NB, Ewalt LC, Lodmell DL: Rabies virus replication in primary murine bone marrow macrophages and in human and murine macrophage-like cell lines: implications for viral persistence. J Virol 1995, 69:764-772.
• [2]Bourhy H, Sureau P, Tordo N: From rabies to rabies-related viruses. Vet Microbiol 1990, 23:115-128.
• [3]Knobel DL, Cleaveland S, Coleman PG, Fevre EM, Meltzer MI, Miranda ME, Shaw A, Zinsstag J, Meslin FX: Re-evaluating the burden of rabies in Africa and Asia. Bull World Health Organ 2005, 83:360-368.
• [4]Xiao C, Rajewsky K: MicroRNA control in the immune system: basic principles. Cell 2009, 136:26-36.
• [5]Brown BD, Naldini L: Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nature reviews 2009, 10:578-585.
• [6]Ambros V: The functions of animal microRNAs. Nature 2004, 431:350-355.
• [7]Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM: bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 2003, 113:25-36.
• [8]Xu P, Vernooy SY, Guo M, Hay BA: The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol 2003, 13:790-795.
• [9]Chen CZ, Li L, Lodish HF, Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science 2004, 303:83-86.
• [10]Ghosh Z, Mallick B, Chakrabarti J: Cellular versus viral microRNAs in host-virus interaction. Nucleic Acids Res 2009, 37:1035-1048.
• [11]Gottwein E, Cullen BR: Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 2008, 3:375-387.
• [12]Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P: Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005, 309:1577-1581.
• [13]Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M: Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 2007, 449:919-922.
• [14]Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, Huang W, Squires K, Verlinghieri G, Zhang H: Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 2007, 13:1241-1247.
• [15]Li Y, Chan EY, Li J, Ni C, Peng X, Rosenzweig E, Tumpey TM, Katze MG: MicroRNA expression and virulence in pandemic influenza virus-infected mice. J Virol 2010, 84:3023-3032.
• [16]Bhomia M, Balakathiresan N, Sharma A, Gupta P, Biswas R, Maheshwari R: Analysis of microRNAs induced by Venezuelan equine encephalitis virus infection in mouse brain. Biochem Biophys Res Commun 2010, 395:11-16.
• [17]Zhao P, Zhao L, Zhang T, Wang H, Qin C, Yang S, Xia X: Changes in microRNA expression induced by rabies virus infection in mouse brains. Microb Pathog 2011, 34:503-512.
• [18]Zhao P, Zhao L, Zhang T, Qi Y, Wang T, Liu K, Wang H, Feng H, Jin H, Qin C, Yang S, Xia X: Innate immune response gene expression profiles in central nervous system of mice infected with rabies virus. Comp Immunol Microbiol Infect Dis 2009, 37:1-3.
• [19]da Huang W, Sherman BT, Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009, 37:1-13.
• [20]Griffin DE: Immune responses to RNA-virus infections of the CNS. Nat Rev Immunol 2003, 3:493-502.
• [21]Lafon M: Modulation of the immune response in the nervous system by rabies virus. Curr Top Microbiol Immunol 2005, 289:239-258.
• [22]Filipowicz W, Bhattacharyya SN, Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature reviews 2008, 9:102-114.
• [23]Lindsay MA: microRNAs and the immune response. Trends Immunol 2008, 29:343-351.
• [24]Pedersen I, David M: MicroRNAs in the immune response. Cytokine 2008, 43:391-394.
• [25]Tsitsiou E, Lindsay MA: microRNAs and the immune response. Curr Opin Pharmacol 2009, 9:514-520.
• [26]Cullen BR: Viral and cellular messenger RNA targets of viral microRNAs. Nature 2009, 457:421-425.
• [27]Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB: Prediction of mammalian microRNA targets. Cell 2003, 115:787-798.
• [28]John B, Sander C, Marks DS: Prediction of human microRNA targets. Methods Mol Biol 2006, 342:101-113.
• [29]Maziere P, Enright AJ: Prediction of microRNA targets. Drug Discov Today 2007, 12:452-458.
• [30]Wang X: El Naqa IM: Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 2008, 24:325-332.
• [31]Peng X, Li Y, Walters KA, Rosenzweig ER, Lederer SL, Aicher LD, Proll S, Katze MG: Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers. BMC Genomics 2009, 10:373. BioMed Central Full Text
• [32]Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF: Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 2006, 312:75-79.
• [33]Linsley PS, Schelter J, Burchard J, Kibukawa M, Martin MM, Bartz SR, Johnson JM, Cummins JM, Raymond CK, Dai H, Chau N, Cleary M, Jackson AL, Carleton M, Lim L: Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol 2007, 27:2240-2252.
• [34]Liu X, Wang T, Wakita T, Yang W: Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology 2010, 398:57-67.
• [35]Jim C, Huang TB, Corson TW, Chua G, Khan S, Gallie BL, Hughes TR, Blencowe BJ, Frey BJ, Morris QD: Using expression profiling data to identify human microRNA targets. Nat Methods 2007, 4:1045-1049.
• [36]Akira S, Uematsu S, Takeuchi O: Pathogen recognition and innate immunity. Cell 2006, 124:783-801.
• [37]Takeuchi O, Akira S: MDA5/RIG-I and virus recognition. Curr Opin Immunol 2008, 20:17-22.
• [38]Taniguchi T, Takaoka A: A weak signal for strong responses: interferon-alpha/beta revisited. Nat Rev Mol Cell Biol 2001, 2:378-386.
• [39]Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X: MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol 2009, 183:2150-2158.
• [40]Brzozka K, Finke S, Conzelmann KK: Inhibition of interferon signaling by rabies virus phosphoprotein P: activation-dependent binding of STAT1 and STAT2. J Virol 2006, 80:2675-2683.
• [41]Zhao L, Toriumi H, Kuang Y, Chen H, Fu ZF: The roles of chemokines in rabies virus infection: overexpression may not always be beneficial. J Virol 2009, 83:11808-11818.
• [42]Zhao L, Toriumi H, Wang H, Kuang Y, Guo X, Morimoto K, Fu ZF: Expression of MIP-1alpha (CCL3) by a recombinant rabies virus enhances its immunogenicity by inducing innate immunity and recruiting dendritic cells and B cells. J Virol 2010, 84:9642-9648.
• [43]Garrington TP, Johnson GL: Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol 1999, 11:211-218.
• [44]Kujime K, Hashimoto S, Gon Y, Shimizu K, Horie T: p38 mitogen-activated protein kinase and c-jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J Immunol 2000, 164:3222-3228.
• [45]Nakamichi K, Saiki M, Sawada M, Takayama-Ito M, Yamamuro Y, Morimoto K, Kurane I: Rabies virus-induced activation of mitogen-activated protein kinase and NF-kappaB signaling pathways regulates expression of CXC and CC chemokine ligands in microglia. J Virol 2005, 79:11801-11812.
• [46]Yan X, Prosniak M, Curtis MT, Weiss ML, Faber M, Dietzschold B, Fu ZF: Silver-haired bat rabies virus variant does not induce apoptosis in the brain of experimentally infected mice. J Neurovirol 2001, 7:518-527.
• [47]Morimoto K, Patel M, Corisdeo S, Hooper DC, Fu ZF, Rupprecht CE, Koprowski H, Dietzschold B: Characterization of a unique variant of bat rabies virus responsible for newly emerging human cases in North America. Proc Natl Acad Sci U S A 1996, 93:5653-5658.
• [48]Faber M, Faber ML, Li J, Preuss MA, Schnell MJ, Dietzschold B: Dominance of a nonpathogenic glycoprotein gene over a pathogenic glycoprotein gene in rabies virus. J Virol 2007, 81:7041-7047.
• [49]Wong ML, Medrano JF: Real-time PCR for mRNA quantitation. Biotechniques 2005, 39:75-85.
• [50]Deng HK, Unutmaz D, KewalRamani VN, Littman DR: Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 1997, 388:296-300.
• [51]Gao X, Gulari E, Zhou X: In situ synthesis of oligonucleotide microarrays. Biopolymers 2004, 73:579-596.
• [52]Zhu Q, Hong A, Sheng N, Zhang X, Matejko A, Jun KY, Srivannavit O, Gulari E, Gao X, Zhou X: microParaflo biochip for nucleic acid and protein analysis. Methods Mol Biol 2007, 382:287-312.
• [53]Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008, 3:1101-1108.
• [54]Huber W, von Heydebreck A, Sultmann H, Poustka A, Vingron M: Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 2002, 18(Suppl 1):S96-S104.
• [55]Smyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004, 3:Article3.