Abstract
Avian-like H5N1 canine influenza virus (CIV) causes severe respiratory infections in dogs. However, the mechanism underlying H5N1 CIV infection in dogs is unknown. The present study aimed to identify differentially expressed miRNAs and mRNAs in the lungs and trachea in H5N1 CIV-infected dogs through a next-generation sequencing-based method. Eighteen 40-day-old beagles were inoculated intranasally with CIV, A/canine/01/Guangdong/2013 (H5N1) at a tissue culture infectious dose 50 (TCID50) of 106, and lung and tracheal tissues were harvested at 3 and 7 d post-inoculation. The tissues were processed for miRNA and mRNA analysis. By means of miRNA-gene expression integrative negative analysis, we found miRNA–mRNA pairs. Lung and trachea tissues showed 138 and 135 negative miRNA–mRNA pairs, respectively. One hundred and twenty negative miRNA–mRNA pairs were found between the different tissues. In particular, pathways including the influenza A pathway, chemokine signaling pathways, and the PI3K-Akt signaling pathway were significantly enriched in all groups in responses to virus infection. Furthermore, dysregulation of miRNA and mRNA expression was observed in the respiratory tract of H5N1 CIV-infected dogs and notably, TLR4 (miR-146), NF-κB (miR-34c) and CCL5 (miR-335), CCL10 (miR-8908-5p), and GNGT2 (miR-122) were found to play important roles in regulating pathways that resist virus infection. To our knowledge, the present study is the first to analyze miRNA and mRNA expression in H5N1 CIV-infected dogs; furthermore, the present findings provide insights into the molecular mechanisms underlying influenza virus infection.
Highlights
The natural host of influenza A virus is wild aquatic birds, the host barrier is not unbreakable, and the virus can be transmitted to other species, including dogs (Klenk, 2014)
H5N1 infections are characterized with a high-fatality rate; in this study, we choose beagles as the animal model of H5N1 infection
We investigated the effect of H5N1 virus infection on miRNA and mRNA, and analyzed the interaction
Summary
The natural host of influenza A virus is wild aquatic birds, the host barrier is not unbreakable, and the virus can be transmitted to other species, including dogs (Klenk, 2014). The first identified CIV was confirmed as subtype H3N8 by sequencing (Crawford et al, 2005). Studies have reported successful experimental infection of CIV in guinea pigs and mice (Tu et al, 2009; Castleman et al, 2010). These findings indicate that dogs may represent a new bridging species for avian and human influenza viruses for interspecies transmission
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