title: Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses.
abstract: Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression, but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and rescued viral infection-induced mouse weight loss, but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection.
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Xihan
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, China.
authors.forename: Jinxiong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, China.
authors.forename: Qianyi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210090, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Qi
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Hou
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210090, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, China.
authors.forename: Hualan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000502:physiology; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000502:physiology; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000628:therapy / Q000821:virology; D031239:Lonicera / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000628:therapy* / Q000821:virology; D018749:RNA, Plant / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; D018749:RNA, Plant