title: H9N2 avian influenza virus enhances the immune responses of BMDCs by down-regulating miR29c.
abstract: Avian influenza virus (AIV) of the subtypes H9 and N2 is well recognised and caused outbreaks-due to its high genetic variability and high rate of recombination with other influenza virus subtypes. The pathogenicity of H9N2 AIV depends on the host immune response. Dendritic cells (DCs) are major antigen presenting cells that can significantly inhibit H9N2 AIV replication. MicroRNAs (miRNAs) influence the ability of DCs to present antigens, as well as the ability of AIVs to infect host cells and replicate. Here, we studied the molecular mechanism underlying the miRNA-mediated regulation of immune function of mouse DCs. We first screened for and verified the induction of miRNAs in DCs after H9N2 AIVstimulation. We also constructed miR29c, miR339 and miR222 over-expression vector and showed that only the induction of miR29c lead to a hugely increased expression of surface marker MHCII and CD40. Whilst the inhibition of miR29c, miR339 and miR222 in mouse DCs would repressed the expression of DCs surface markers. Moreover, we found that miR29c stimulation not only up-regulate MHCII and CD40, but also enhance the ability of DCs to activate lymphocytes and secrete cytokines IL-6 or TNF-a. Furthermore, we found that Tarbp1 and Rfx7 were targeted and repressed by miR29c. Finally, we revealed that the inhibition of miR29c marvelously accelerated virus replication. Together, our data shed new light on the roles and mechanisms of miR29c in regulating DC function and suggest new strategies for combating AIVs.
authors.affiliation: College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: linjian@njau.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: 2014816155@njau.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.affiliation: College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: 2013816153@njau.edu.cn.
authors.forename: Ya T
authors.initials: YT
authors.lastname: Chen
authors.affiliation: College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: keyunzhang@njau.edu.cn.
authors.forename: Ke Y
authors.initials: KY
authors.lastname: Zhang
authors.affiliation: College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: zengyan@njau.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address: zxbyq@njau.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000276:immunology / Q000821:virology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D014774:Virulence; D014779:Virus Replication; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D035683:MicroRNAs; D020320:Oligoribonucleotides, Antisense; D016601:RNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000099253:Trans-Activation Responsive RNA-Binding Protein; C547014:MIRN29 microRNA, mouse; C577686:interleukin-6, mouse
keywords: Dendritic cells; H9N2 AIV; Immune regulation; Target gene; miR29c