MiRNA profile in mice lung after influenza A infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE70125 | GEO | 2015/06/22
SECONDARY ACCESSION(S): PRJNA287682
REPOSITORIES: GEO
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Project description:The regulation of host defense against influenza A viruses (IAVs) infection has attracted much attention, especially for type I interferon (IFN)-mediated innate response. Here we revealed that miR-93 expression was significantly downregulated in Alveolar epithelial type II cells (AT2) upon IAVs infection through RIG-I/JNK pathway. Inhibition of miR-93 was found to suppress host antiviral innate response by facilitating type I IFN effector signaling, and JAK1 was identified to be directly targeted by miR-93. Importantly, in vivo administration of miR-93 antagomiR significantly inhibited miR-93 expression and markedly suppressed IAVs infection, which in turn prevented the death of IAVs infected mice. Hence, the inducible downregulation of miR-93 suppress IAVs infection by upregulation IFN-JAK-STAT effector pathway, and in vivo inhibition of miR-93 bears considerable therapeutic potential for suppressing IAVs infection. The miRNA profiling in mice lung was measured at 24 and 36 hours after gave each mouse 50µl of influenza A (50 µl of 10-6 TCID50/µl) via retropharyngeal instillation. Three mice were performed at each time (24 or 36 hours) and RNA from different donors was mixed before determination.
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Project description: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 improved 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 both 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. Screening and profiling of known plant microRNA in HS and HS decoction
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Project description: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 improved 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 both 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.
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