title: Induction of the cellular miR-29c by influenza virus inhibits the innate immune response through protection of A20 mRNA.
abstract: Influenza A viruses (IAVs) are negative-sense, single-stranded, segmented RNA viruses, which primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. MicroRNAs (miRNAs) represent a family of small noncoding RNAs controlling translation and transcription of many genes. The human miR-29 family of miRNAs has three mature members, miR-29a, miR-29b, and miR-29c. Recent studies have revealed that miR-29 is involved in regulation of the innate and adaptive immune responses. However, the function of miR-29 in the immune response to IAV infection remains to be further explored. Our previous study has shown that miR-29 family members are up-regulated during IAV infection, especially miR-29c. Here we report that miR-29c is involved in inhibition of IAV-induced innate immune responses. We found that posttranscriptional regulation was involved in IAV-induced A20 expression in A549 cells. Consistent with a previous report, miR-29c functionally protected A20 transcripts in A549 cells. Overexpression of miR-29c with miR-29c mimic enhanced IAV-induced A20 protein expression and conversely that miR-29c inhibitor significantly blocked IAV-induced A20 protein expression in A549 cells. Furthermore, functional results showed that IAV-induced miR-29c expression correlated with decreased NF-κB activity and expression of several antiviral and proinflammatory cytokines via up-regulation of A20. Together, the findings indicate a new role of miR-29c in IAV infection and suggest its induction may contribute to counteract the innate immune response.
authors: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 130062 Changchun, PR China.
authors: Xiaoyang
authors: X
authors: Zhang
authors: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 130062 Changchun, PR China.
authors: Chunyan
authors: C
authors: Dong
authors: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 130062 Changchun, PR China.
authors: Xiaoning
authors: X
authors: Sun
authors: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, 130062 Changchun, PR China.
authors: Zhongyi
authors: Z
authors: Li
authors: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 130062 Changchun, PR China.
authors: Maolin
authors: M
authors: Zhang
authors: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 130062 Changchun, PR China.
authors: Zhenhong
authors: Z
authors: Guan
authors: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, 130062 Changchun, PR China. Electronic address: duan_ming@jlu.edu.cn.
authors: Ming
authors: M
authors: Duan
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D009981:Influenza B virus / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014775:Virus Activation / Q000502:physiology*
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: A20; Influenza A virus; Innate immune response; miR-29c