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Journal of Integrative Agriculture  2019, Vol. 18 Issue (7): 1421-1427    DOI: 10.1016/S2095-3119(18)62134-3
Special Focus: Animal influenza virus Advanced Online Publication | Current Issue | Archive | Adv Search |
Regulation of influenza virus infection by microRNAs
ZOU Zhong1, 2, 3*, GONG Wen-xiao1, 2, 3*, HUANG Kun1, 2, SUN Xiao-mei1, 2, 3, JIN Mei-lin1, 2, 3  
1 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, P.R.China
2 College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, P.R.China
3 Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture and Rural Affairs, Wuhan 430070, P.R.China
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MicroRNAs (miRNAs) are small noncoding RNAs of 18–25 nucleotides (nt) in length that represent key regulators of many normal cellular functions through the inhibition of mRNA translation and mRNA degradation.  To date, over 2 500 mature miRNAs have been identified in plants, animals and several types of viruses.  Influenza A virus (IAV), which is a negative-sense, single-stranded RNA virus, does not encode viral miRNA.  However, IAV infection can alter the expression of host miRNAs, either in cell culture or in host.  In turn, host miRNAs regulate IAV life cycle through directly binding to IAV genome or indirectly targeting host factors associated with viral replication.  In this review, we briefly summarized the role and significance of miRNA in relation to IAV pathogenesis.  Understanding the role of cellular miRNAs during viral infection may be beneficial to the identification of novel therapeutic strategies to block IAV replication.
Keywords:  microRNAs        influenza A virus        pathogenesis        therapeutic strategies  
Received: 21 August 2018   Online: 07 November 2018   Accepted: 01 July 2019
Fund: This research was supported by the National Key Research and Development Program of China (2016YFD0501600).
Corresponding Authors:  Correspondence JIN Mei-lin, E-mail:    
About author:  * These authors contributed equally to this study.

Cite this article: 

ZOU Zhong, GONG Wen-xiao, HUANG Kun, SUN Xiao-mei, JIN Mei-lin. 2019. Regulation of influenza virus infection by microRNAs. Journal of Integrative Agriculture, 18(7): 1421-1427.

Bartel D P. 2004. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.
Buggele W A, Johnson K E, Horvath C M. 2012. Influenza A virus infection of human respiratory cells induces primary microRNA expression. The Journal of Biological Chemistry, 287, 31027–31040.
Chan P K. 2002. Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clinical Infectious Diseases, 34(Suppl.2), S58–S64.
Chen X, Zhou L, Peng N, Yu H, Li M, Cao Z, Lin Y, Wang X, Li Q, Wang J, She Y, Zhu C, Lu M, Zhu Y, Liu S. 2017. MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory factor-5 expression and cytokine storm induction. The Journal of Biological Chemistry, 292, 21291–21303.
Deng Y, Yan Y, Tan K S, Liu J, Chow V T, Tao Z Z, Wang D Y. 2017. MicroRNA-146a induction during influenza H3N2 virus infection targets and regulates TRAF6 levels in human nasal epithelial cells (hNECs). Experimental Cell Research, 352, 184–192.
Dong C, Sun X, Guan Z, Zhang M, Duan M. 2017. Modulation of influenza A virus replication by microRNA-9 through targeting MCPIP1. Journal of Medical Virology, 89, 41–48.
Gui S, Chen X, Zhang M, Zhao F, Wan Y, Wang L, Xu G, Zhou L, Yue X, Zhu Y, Liu S. 2015. Mir-302c mediates influenza A virus-induced IFNβ expression by targeting NF-κB inducing kinase. FEBS Letters, 589, 4112–4118.
He T, Feng G, Chen H, Wang, Wang Y. 2009. Identification of host encoded microRNAs interacting with novel swine-origin influenza A (H1N1) virus and swine influenza virus. Bioinformation, 4, 112–118.
Hsu A C, Dua K, Starkey M R, Haw T J, Nair P, Nichol K, Zammit N, Grey S T, Baines K J, Foster P S, Hansbro P M, Wark P A. 2017. MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD. JCI Insight, 2, e90443.
Hu Y, Jiang L, Lai W, Qin Y, Zhang T, Wang S, Ye X. 2016. MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity. The Journal of General Virology, 97, 27–38.
Ingle H, Kumar S, Raut A A, Mishra A, Kulkarni D D, Kameyama T, Takaoka A, Akira S, Kumar H. 2015. The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication. Science Signaling, 8, ra126.
Khongnomnan K, Makkoch J, Poomipak W, Poovorawan Y, Payungporn S. 2015. Human miR-3145 inhibits influenza A viruses replication by targeting and silencing viral PB1 gene. Experimental Biology and Medicine, 240, 1630–1639.
Lee R C, Feinbaum R L, Ambros V. 1993. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–854.
Li J, Arevalo M T, Diaz-Arevalo D, Chen Y, Choi J G, Zeng M. 2015. Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA. Journal of Controlled Release: Official Journal of the Controlled Release Society, 207, 70–76.
Li X, Fu Z, Liang H, Wang Y, Qi X, Ding M, Sun X, Zhou Z, Huang Y, Gu H, Li L, Chen X, Li D, Zhao Q, Liu F, Wang H, Wang J, Zen K, Zhang C Y. 2018. H5N1 influenza virus-specific miRNA-like small RNA increases cytokine production and mouse mortality via targeting poly(rC)-binding protein 2. Cell Research, 28, 157–171.
Loveday E K, Diederich S, Pasick J, Jean F. 2015. Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin. The Journal of General Virology, 96, 30–39.
Ma Y J, Yang J, Fan X L, Zhao H B, Hu W, Li Z P, Yu G C, Ding X R, Wang J Z, Bo X C, Zheng X F, Zhou Z, Wang S Q. 2012. Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells. Journal of Cellular and Molecular Medicine, 16, 2539–2546.
Maemura T, Fukuyama S, Sugita Y, Lopes T J S, Nakao T, Noda T, Kawaoka Y. 2018. Lung-derived exosomal miR-483-3p regulates the innate immune response to influenza virus infection. The Journal of Infectious Diseases, 217, 1372–1382.
Manicassamy B, Medina R A, Hai R, Tsibane T, Stertz S, Nistal-Villan E, Palese P, Basler C F, Garcia-Sastre A. 2010. Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines. PLoS Pathogens, 6, e1000745.
Moran J, Ramirez-Martinez G, Jimenez-Alvarez L, Cruz A, Perez-Patrigeon S, Hidalgo A, Orozco L, Martinez A, Padilla-Noriega L, Avila-Moreno F, Cabello C, Granados J, Ortiz-Quintero B, Ramirez-Venegas A, Ruiz-Palacios G M, Zlotnik A, Merino E, Zuniga J. 2015. Circulating levels of miR-150 are associated with poorer outcomes of
A/H1N1 infection. Experimental and Molecular Pathology, 99, 253–261.
Othumpangat S, Noti J D, Blachere F M, Beezhold D H. 2013. Expression of non-structural-1A binding protein in lung epithelial cells is modulated by miRNA-548an on exposure to influenza A virus. Virology, 447, 84–94.
Peng S, Wang J, Wei S, Li C, Zhou K, Hu J, Ye X, Yan J, Liu W, Gao G F, Fang M, Meng S. 2018. Endogenous cellular micrornas mediate antiviral defense against influenza A virus. Molecular Therapy Nucleic Acids, 10, 361–375.
Pichulik T, Khatamzas E, Liu X, Brain O, Delmiro Garcia M, Leslie A, Danis B, Mayer A, Baban D, Ragoussis J, Weber A N, Simmons A. 2016. Pattern recognition receptor mediated downregulation of microRNA-650 fine-tunes MxA expression in dendritic cells infected with influenza A virus. European Journal of Immunology, 46, 167–177.
Pilakka-Kanthikeel S, Saiyed Z M, Napuri J, Nair M P. 2011. MicroRNA: Implications in HIV, a brief overview. Journal of Neurovirology, 17, 416–423.
Rosenberger C M, Podyminogin R L, Diercks A H, Treuting P M, Peschon J J, Rodriguez D, Gundapuneni M, Weiss M J, Aderem A. 2017. miR-144 attenuates the host response to influenza virus by targeting the TRAF6-IRF7 signaling axis. PLoS Pathogens, 13, e1006305.
Samji T. 2009. Influenza A: Understanding the viral life cycle. The Yale Journal of Biology and Medicine, 82, 153–159.
Song H, Wang Q, Guo Y, Liu S, Song R, Gao X, Dai L, Li B, Zhang D, Chen J. 2013. Microarray analysis of microRNA expression in peripheral blood mononuclear cells of critically ill patients with influenza A (H1N1). BMC Infectious Diseases, 13, 257.
Song L, Liu H, Gao S, Jiang W, Huang W. 2010. Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells. Journal of Virology, 84, 8849–8860.
Tambyah P A, Sepramaniam S, Mohamed Ali J, Chai S C, Swaminathan P, Armugam A, Jeyaseelan K. 2013. microRNAs in circulation are altered in response to influenza A virus infection in humans. PLoS ONE, 8, e76811.
Tang X, Zhang H, Song Y, Zhou D, Wang J. 2016. Hemagglutinin-targeting artificial microRNAs expressed by adenovirus protect mice from different clades of H5N1 infection. Molecular Therapy Nucleic Acids, 5, e311.
Tomankova T, Petrek M, Kriegova E. 2010. Involvement of microRNAs in physiological and pathological processes in the lung. Respiratory Research, 11, 159.
Te Velthuis A J, Fodor E. 2016. Influenza virus RNA polymerase: Insights into the mechanisms of viral RNA synthesis. Nature Reviews (Microbiology), 14, 479–493.
Wang J W, Li K, Hellermann G, Lockey R F, Mohapatra S, Mohapatra S. 2011. Regulating the regulators: MicroRNA and asthma. The World Allergy Organization Journal, 4, 94–103.
Wang K, Lai C, Gu H, Zhao L, Xia M, Yang P, Wang X. 2017. miR-194 inhibits innate antiviral immunity by targeting FGF2 in influenza H1N1 virus infection. Frontiers in Microbiology, 8, 2187.
Wang Y, Brahmakshatriya V, Zhu H, Lupiani B, Reddy S M, Yoon B J, Gunaratne P H, Kim J H, Chen R, Wang J, Zhou H. 2009. Identification of differentially expressed miRNAs in chicken lung and trachea with avian influenza virus infection by a deep sequencing approach. BMC Genomics, 10, 512.
Waring B M, Sjaastad L E, Fiege J K, Fay E J, Reyes I, Moriarity B, Langlois R A. 2018. MicroRNA-based attenuation of influenza virus across susceptible hosts. Journal of Virology, 92, 01741-17.
Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nature Immunology, 5, 730–737.
Zhang H, Li Z, Li Y, Liu Y, Liu J, Li X, Shen T, Duan Y, Hu M, Xu D. 2013. A computational method for predicting regulation of human microRNAs on the influenza virus genome. BMC Systems Biology, 7(Suppl.2), S3.
Zhang H, Tang X, Zhu C, Song Y, Yin J, Xu J, Ertl H C, Zhou D. 2015. Adenovirus-mediated artificial microRNAs targeting matrix or nucleoprotein genes protect mice against lethal influenza virus challenge. Gene Therapy, 22, 653–662.
Zhang S, Wang R, Su H, Wang B, Sizhu S, Lei Z, Jin M, Chen H, Cao J, Zhou H. 2017. Sus scrofa miR-204 and miR-4331 negatively regulate swine H1N1/2009 influenza a virus replication by targeting viral HA and NS, respectively. International Journal of Molecular Sciences, 18, 749.
Zhang X, Dong C, Sun X, Li Z, Zhang M, Guan Z, Duan M. 2014. Induction of the cellular miR-29c by influenza virus inhibits the innate immune response through protection of A20 mRNA. Biochemical and Biophysical Research Communications, 450, 755–761.
Zhao L, Zhu J, Zhou H, Zhao Z, Zou Z, Liu X, Lin X, Zhang X, Deng X, Wang R, Chen H, Jin M. 2015. Identification of cellular microRNA-136 as a dual regulator of RIG-I-mediated innate immunity that antagonizes H5N1 IAV replication in A549 cells. Scientific Reports, 5, 14991.
Zhou Z, Li X, Liu J, Dong L, Chen Q, Liu J, Kong H, Zhang Q, Qi X, Hou D, Zhang L, Zhang G, Liu Y, Zhang Y, Li J, Wang J, Chen X, Wang H, Zhang J, Chen H, et al. 2015. Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses. Cell Research, 25, 39–49.
Zhu Z, Qi Y, Ge A, Zhu Y, Xu K, Ji H, Shi Z, Cui L, Zhou M. 2014. Comprehensive characterization of serum microRNA profile in response to the emerging avian influenza A (H7N9) virus infection in humans. Viruses, 6, 1525–1539.
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