The Differential Expression and Possible Function of Long Noncoding RNAs in Liver Cells Infected by Dengue Virus

Xiao-Jun Wang Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China;
Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China

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Shi-Chen Jiang Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China;

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Hai-Xia Wei Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China;

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Sheng-Qun Deng Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China;

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Cheng He Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China;

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Hong-Juan Peng Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China;

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The function of long noncoding RNAs (lncRNAs) in liver injury resulted by dengue virus (DENV) infection have not yet been explored. The differential expression profiles of lncRNAs (as well as mRNAs) in the L-02 liver cells infected by DENV1, DENV2, or uninfected were compared and analyzed after a high throughput RNA seq. The significantly up-regulated and down-regulated lncRNAs (or mRNAs) resulted by DENV infection were identified with a cutoff value at log2 (ratio) ≥ 1.5 and log2 (ratio) ≤ −1.5 (ratio = the reads of the lncRNAs or mRNAs from the infection groups divided by the reads from the control group). Several differentially expressed lncRNAs were verified with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Target gene analysis, pre-miRNA prediction, and the lncRNA-mRNA co-expression network construction were performed to predict the function of the differentially expressed lncRNAs. The differentially expressed lncRNAs were associated with biosynthesis, DNA/RNA related processes, inhibition of estrogen signaling pathway, sterol biosynthetic process, protein dimerization activity, vesicular fraction in DENV1 infection group; and with protein secretion, methyltransferase process, host cell cytoskeleton reorganization and the small GTPase Ras superfamily, inhibition of cell proliferation, induction of apoptosis in DENV2 infection. LncRNAs might be novel diagnostic markers and targets for further researches on dengue infection and liver injury resulted by dengue virus.

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Author Notes

Address correspondence to Hong-Juan Peng, Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, 1023 South Shatai Rd, Guangzhou, Guangdong Province 510515, China. E-mail: hongjuan@smu.edu.cn

Financial support: This work was supported by the funding of the National Natural Science Foundation of China (81572012), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2014), the National key research and development plan project (2017YFD0500403), the Guangdong Provincial Natural Science Foundation Key Project (2016A030311025),and Guangzhou health and medical collaborative innovation major special project(201604020011) to H.-J. P.; the special fund of public interest research and capacity building of Guangdong Province (2014A020212506) and the Natural Science Found of Guangdong Medical University (M2014008) and the grant from Dongguan Key Laboratory of Environmental Medicine. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Authors’ addresses: Xiao-Jun Wang, Shi-Chen Jiang, Hai-Xia Wei, Sheng-Qun Deng, Cheng He, and Hong-Juan Peng, Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China, E-mails: erxiao0401@163.com, 476786574@qq.com, weihaixia2012@sina.com, 874337111@qq.com, hechengchoice@163.com, and hongjuan@smu.edu.cn.

  • 1.

    Guzmán MG, Kourí G, 2002. Dengue: an update. Lancet Infect Dis 2: 3342.

  • 2.

    Mishra G, Jain A, Prakash O, Prakash S, Kumar R, Garg RK, Pandey N, Singh M, 2015. Molecular characterization of dengue viruses circulating during 2009–2012 in Uttar Pradesh, India. J Med Virol 87: 6875.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Bhatt S et al. 2013. The global distribution and burden of dengue. Nature 496: 504507.

  • 4.

    Thongtan T, Panyim S, Smith DR, 2004. Apoptosis in dengue virus infected liver cell lines HepG2 and Hep3B. J Med Virol 72: 436444.

  • 5.

    Seneviratne SL, Malavige GN, de Silva HJ, 2006. Pathogenesis of liver involvement during dengue viral infections. Trans R Soc Trop Med Hyg 100: 608614.

  • 6.

    Huerre MR et al. 2001. Liver histopathology and biological correlates in five cases of fatal dengue fever in Vietnamese children. Virchows Arch 438: 107115.

  • 7.

    Samanta J, Sharma V, 2015. Dengue and its effects on liver. World J Clin Cases 3: 125131.

  • 8.

    Roy A, Sarkar D, Chakraborty S, Chaudhuri J, Ghosh P, Chakraborty S, 2013. Profile of hepatic involvement by dengue virus in dengue infected children. N Am J Med Sci 5: 480485.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Mohan B, Patwari AK, Anand VK, 2000. Hepatic dysfunction in childhood dengue infection. J Trop Pediatr 46: 4043.

  • 10.

    Wang XJ, Wei HX, Jiang SC, He C, Xu XJ, Peng HJ, 2016. Evaluation of aminotransferase abnormality in dengue patients: a meta analysis. Acta Trop 156: 130136.

  • 11.

    Couvelard A, Marianneau P, Bedel C, Drouet MT, Vachon F, Hénin D, Deubel V, 1999. Report of a fatal case of dengue infection with hepatitis: demonstration of dengue antigens in hepatocytes and liver apoptosis. Hum Pathol 30: 11061110.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Quagliata L, Terracciano LM, 2014. Liver diseases and long non-coding RNAs: new insight and perspective. Front Med (Lausanne) 1: 35.

  • 13.

    Guerrieri F, 2015. Long non-coding RNAs era in liver cancer. World J Hepatol 7: 19711973.

  • 14.

    Tripathi V et al. 2010. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39: 925938.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Pan YF, Qin T, Feng L, Yu ZJ, 2013. Expression profile of altered long non-coding RNAs in patients with HBV-associated hepatocellular carcinoma. J Huazhong Univ Sci Technolog Med Sci 33: 96101.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Xu D, Yang F, Yuan JH, Zhang L, Bi HS, Zhou CC, Liu F, Wang F, Sun SH, 2013. Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/beta-catenin signaling. Hepatology 58: 739751.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Guo RN, Lin JY, Li LH, Ke CW, He JF, Zhong HJ, Zhou HQ, Peng ZQ, Yang F, Liang WJ, 2014. The prevalence and endemic nature of dengue infections in Guangdong, south China: an epidemiological, serological, and etiological study from 2005–2011. PLoS One 9: e85596.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Luo L, Liang HY, Hu YS, Liu WJ, Wang YL, Jing QL, Zheng XL, Yang ZC, 2012. Epidemiological, virological, and entomological characteristics of dengue from 1978 to 2009 in Guangzhou, China. J Vector Ecol 37: 230240.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Ramakrishnan MA, 2016. Determination of 50% endpoint titer using a simple formula. World J Virol 5: 8586.

  • 20.

    Groves IJ, Reeves MB, Sinclair JH, 2009. Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic ‘pre-immediate-early’ repression of viral gene expression mediated by histone post-translational modification. J Gen Virol 90: 23642374.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Pattanakitsakul SN, Rungrojcharoenkit K, Kanlaya R, Sinchaikul S, Noisakran S, Chen ST, Malasit P, Thongboonkerd V, 2007. Proteomic analysis of host responses in HepG2 cells during dengue virus infection. J Proteome Res 6: 45924600.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Jung KH, Das A, Chai JC, Kim SH, Morya N, Park KS, Lee YS, Chai YG, 2015. RNA sequencing reveals distinct mechanisms underlying BET inhibitor JQ1-mediated modulation of the LPS-induced activation of BV-2 microglial cells. J Neuroinflammation 12: 36.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    O’Keeffe G, Hammel S, Owens RA, Keane TM, Fitzpatrick DA, Jones GW, Doyle S, 2014. RNA-seq reveals the pan-transcriptomic impact of attenuating the gliotoxin self-protection mechanism in Aspergillus fumigatus. BMC Genomics 15: 894.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL, 2013. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14: R36.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Langmead B, Trapnell C, Pop M, Salzberg SL, 2009. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.

  • 26.

    Yusuf NH, Ong WD, Redwan RM, Latip MA, Kumar SV, 2015. Discovery of precursor and mature microRNAs and their putative gene targets using high-throughput sequencing in pineapple (Ananas comosus var. comosus). Gene 571: 7180.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Farazi TA, Hoell JI, Morozov P, Tuschl T, 2013. MicroRNAs in human cancer. Adv Exp Med Biol 774: 120.

  • 28.

    Cai X, Cullen BR, 2007. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA 13: 313316.

  • 29.

    Wilusz JE, Sunwoo H, Spector DL, 2009. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23: 14941504.

  • 30.

    Xiong Y, Chen S, Liu L, Zhao Y, Lin W, Ni J, 2013. Increased serum microRNA-155 level associated with nonresponsiveness to hepatitis B vaccine. Clin Vaccine Immunol 20: 10891091.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Sherman BT, Huang da W, Tan Q, Guo Y, Bour S, Liu D, Stephens R, Baseler MW, Lane HC, Lempicki RA, 2007. DAVID knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics 8: 426.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Wang K, Guo WX, Li N, Gao CF, Shi J, Tang YF, Shen F, Wu MC, Liu SR, Cheng SQ, 2015. Serum LncRNAs profiles serve as novel potential biomarkers for the diagnosis of HBV-positive hepatocellular carcinoma. PLoS One 10: e0144934.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Landeras-Bueno S, Ortín J, 2016. Regulation of influenza virus infection by long non-coding RNAs. Virus Res 212: 7884.

  • 34.

    Zhang Q, Chen CY, Yedavalli VS, Jeang KT, 2013. NEAT1 long noncoding RNA and paraspeckle bodies modulate HIV-1 posttranscriptional expression. MBio 4: e00596e00612.

  • 35.

    Yin Z, Guan D, Fan Q, Su J, Zheng W, Ma W, Ke C, 2013. lncRNAs expression signatures in response to enterovirus 71 infection. Biochem Biophys Res Commun 430: 629633.

  • 36.

    Mattick JS, Amaral PP, Dinger ME, Mercer TR, Mehler MF, 2009. RNA regulation of epigenetic processes. BioEssays 31: 5159.

  • 37.

    Ahanda ML, Ruby T, Wittzell H, Bed’Hom B, Chaussé AM, Morin V, Oudin A, Chevalier C, Young JR, Zoorob R, 2009. Non-coding RNAs revealed during identification of genes involved in chicken immune responses. Immunogenetics 61: 5570.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Peng X et al. 2010. Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling. MBio 1: e00206e00210.

  • 39.

    Lee LK, Gan VC, Lee VJ, Tan AS, Leo YS, Lye DC, 2012. Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity. PLoS Negl Trop Dis 6: e1676.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Martina BE, Koraka P, Osterhaus AD, 2009. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22: 564581.

  • 41.

    Ouyang J et al. 2014. NRAV, a long noncoding RNA, modulates antiviral responses through suppression of interferon-stimulated gene transcription. Cell Host Microbe 16: 616626.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Carpenter S et al. 2013. A long noncoding RNA mediates both activation and repression of immune response genes. Science 341: 789792.

  • 43.

    Saayman S, Ackley A, Turner AW, Famiglietti M, Bosque A, Clemson M, Planelles V, Morris KV, 2014. An HIV-encoded antisense long noncoding RNA epigenetically regulates viral transcription. Mol Ther 22: 11641175.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Ding YZ, Zhang ZW, Liu YL, Shi CX, Zhang J, Zhang YG, 2016. Relationship of long noncoding RNA and viruses. Genomics 107: 150154.

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