PMID- 28382020 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 8 DP - 2017 TI - H9N2 Avian Influenza Virus Protein PB1 Enhances the Immune Responses of Bone Marrow-Derived Dendritic Cells by Down-Regulating miR375. PG - 287 LID - 10.3389/fmicb.2017.00287 [doi] LID - 287 AB - Polymerase basic protein 1 (PB1), the catalytic core of the influenza A virus RNA polymerase complex, is essential for viral transcription and replication. Dendritic cells (DCs) possess important antigen presenting ability and a crucial role in recognizing and clearing virus. MicroRNA (miRNA) influence the development of DCs and their ability to present antigens as well as the ability of avian influenza virus (AIV) to infect host cells and replicate. Here, we studied the molecular mechanism underlying the miRNA-mediated regulation of immune function in mouse DCs. We first screened for and verified the induction of miRNAs in DCs after PB1 transfection. Results showed that the viral protein PB1 down-regulated the expression of miR375, miR146, miR339, and miR679 in DCs, consistent with the results of H9N2 virus treatment; however, the expression of miR222 and miR499, also reduced in the presence of PB1, was in contrast to the results of H9N2 virus treatment. Our results suggest that PB1 enhanced the ability of DCs to present antigens, activate lymphocytes, and secrete cytokines, while miR375 over-expression repressed activation of DC maturation. Nevertheless, PB1 could not promote DC maturation once miR375 was inhibited. Finally, we revealed that PB1 inhibited the P-Jnk/Jnk signaling pathway, but activated the p-Erk/Erk signaling pathway. While inhibition of miR375 -activated the p-Erk/Erk and p-p38/p38 signaling pathway, but repressed the P-Jnk/Jnk signaling pathway. Taken together, results of our studies shed new light on the roles and mechanisms of PB1 and miR375 in regulating DC function and suggest new strategies for combating AIV. FAU - Lin, Jian AU - Lin J AD - Department of Zoology, College of Life Science, Nanjing Agricultural University Jiangsu, China. FAU - Xia, Jing AU - Xia J AD - Department of Zoology, College of Life Science, Nanjing Agricultural University Jiangsu, China. FAU - Tu, Chong Z AU - Tu CZ AD - Department of Histoembryology, College of Veterinary Medicine, Nanjing Agricultural University Jiangsu, China. FAU - Zhang, Ke Y AU - Zhang KY AD - Department of Zoology, College of Life Science, Nanjing Agricultural University Jiangsu, China. FAU - Zeng, Yan AU - Zeng Y AD - Department of Zoology, College of Life Science, Nanjing Agricultural University Jiangsu, China. FAU - Yang, Qian AU - Yang Q AD - Department of Zoology, College of Life Science, Nanjing Agricultural University Jiangsu, China. LA - eng PT - Journal Article DEP - 20170322 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC5360757 OTO - NOTNLM OT - H9N2 AIV OT - PB1 OT - dendritic cells OT - immune regulation OT - miRNA EDAT- 2017/04/07 06:00 MHDA- 2017/04/07 06:01 PMCR- 2017/03/22 CRDT- 2017/04/07 06:00 PHST- 2016/09/26 00:00 [received] PHST- 2017/02/13 00:00 [accepted] PHST- 2017/04/07 06:00 [entrez] PHST- 2017/04/07 06:00 [pubmed] PHST- 2017/04/07 06:01 [medline] PHST- 2017/03/22 00:00 [pmc-release] AID - 10.3389/fmicb.2017.00287 [doi] PST - epublish SO - Front Microbiol. 2017 Mar 22;8:287. doi: 10.3389/fmicb.2017.00287. eCollection 2017.