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.

Microarray analysis of infectious bronchitis virus infection of chicken primary dendritic cells

“…Unsurprisingly, major changes in miRNA expression have been shown to be the underlying mechanism triggering the host immune response [24]. For example, miR29c was found to enhance the immune function of DCs, whereas miR375 was suggested to attenuate the antigen-presenting ability of mouse DCs [25, 26]. In addition to evoking an immune response, miRNAs may also shape host–virus interactions and defend against viral infection [27, 28].…”

Common microRNA–mRNA Interactions in Different Newcastle Disease Virus-Infected Chicken Embryonic Visceral Tissues

“…miRNAs are important cellular regulatory factors that regulate post-transcriptional gene expression by degrading their transcription or blocking translation [ 14 , 15 , 16 , 17 , 18 ]. The roles of miRNAs in the regulation of virus infection, such as Avian influenza virus (AIV), Infectious Bursal disease virus (IBDV), Marek’s disease virus (MDV), Hepatitis C virus (HCV), etc., have all been previously identified [ 19 , 20 , 21 , 22 ]. In addition to affecting gene expression in the host, miRNAs can bind viral genes to regulate viral replication [ 23 , 24 ].…”

Analysis of the microRNA expression profiles of chicken dendritic cells in response to H9N2 avian influenza virus infection

“…Differential miRNA expression profiles have been observed in chicken lungs during H5N3 AIV infection [ 5 ]. In addition, H9N2 AIV infection has been shown to activate the immune responses of mouse and avian dendritic cells by regulating the expression of miRNAs [ 6 – 8 ]. All of these studies suggest that miRNAs play an important role in the complex interactions occurring between influenza viruses and their hosts [ 9 ].…”