Abstract

BackgroundAvian influenza virus (AIV) outbreaks are worldwide threats to both poultry and humans. Our previous study suggested microRNAs (miRNAs) play significant roles in the regulation of host response to AIV infection in layer chickens. The objective of this study was to test the hypothesis if genetic background play essential role in the miRNA regulation of AIV infection in chickens and if miRNAs that were differentially expressed in layer with AIV infection would be modulated the same way in broiler chickens. Furthermore, by integrating with parallel mRNA expression profiling, potential molecular mechanisms of host response to AIV infection can be further exploited.ResultsTotal RNA isolated from the lungs of non-infected and low pathogenic H5N3 infected broilers at four days post-infection were used for both miRNA deep sequencing and mRNA microarray analyses. A total of 2.6 M and 3.3 M filtered high quality reads were obtained from infected and non-infected chickens by Solexa GA-I Sequencer, respectively. A total of 271 miRNAs in miRBase 16.0 were identified and one potential novel miRNA was discovered. There were 121 miRNAs differentially expressed at the 5% false discovery rate by Fisher’s exact test. More miRNAs were highly expressed in infected lungs (108) than in non-infected lungs (13), which was opposite to the findings in layer chickens. This result suggested that a different regulatory mechanism of host response to AIV infection mediated by miRNAs might exist in broiler chickens. Analysis using the chicken 44 K Agilent microarray indicated that 508 mRNAs (347 down-regulated) were differentially expressed following AIV infection.ConclusionsA comprehensive analysis combining both miRNA and targeted mRNA gene expression suggests that gga-miR-34a, 122–1, 122–2, 146a, 155, 206, 1719, 1594, 1599 and 451, and MX1, IL-8, IRF-7, TNFRS19 are strong candidate miRNAs or genes involved in regulating the host response to AIV infection in the lungs of broiler chickens. Further miRNA or gene specific knock-down assay is warranted to elucidate underlying mechanism of AIV infection regulation in the chicken.

Highlights

  • Avian influenza virus (AIV) outbreaks are worldwide threats to both poultry and humans

  • All reads with a perfect match to mature miRNA sequences from chicken deposited in miRBase version 16.0 [22,23,24] with insertions or deletions of 1–4 nucleotides at the 5’ and 3’ ends of miRNAs were considered to represent Dicer-processing products from each of the chicken miRNA precursors [20]

  • Gga-miR-142-3p was down-regulated in layers and up-regulated in broilers, which indicate that host immune response to AIV infection mediated by gga-miR-142-3p in broiler chickens may be different from layer. Other factors such as time of challenge may contribute to great miRNA difference between broilers and layers, these results strongly suggest that genetic backgrounds play a vital role in the regulation of miRNAs during AIV infection in chickens

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Summary

Introduction

Avian influenza virus (AIV) outbreaks are worldwide threats to both poultry and humans. Our previous study suggested microRNAs (miRNAs) play significant roles in the regulation of host response to AIV infection in layer chickens. By integrating with parallel mRNA expression profiling, potential molecular mechanisms of host response to AIV infection can be further exploited. Avian influenza virus (AIV) infection is a world-wide threat to both human and avian species. AIV causes an infection of the respiratory tract of the host, triggering a cascade of innate and adaptive immune responses. Understanding host response to AIV infection and chicken-virus interaction is essential to the poultry industry, and provides key insights into the prophylactic and therapeutic protection for other influenza hosts including humans

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