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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Integrated analysis of microRNA expression and mRNA transcriptome in lungs of avian influenza virus infected broilers
Ying Wang1, Vinayak Brahmakshatriya, Blanca Lupiani
1Department of Animal Science, University of California, Davis, CA 95616, USA.
Background:
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. 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.
Results:
Total 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.
Conclusions:
A 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.
Insights
Genetic background influences avian influenza virus (AIV) response in chickens. Broiler chickens show different microRNA (miRNA) expression patterns compared to layers, highlighting distinct regulatory mechanisms against AIV infection.
Area of Science:
- * Comparative genomics and molecular biology
- * Avian virology and immunology
Background:
- * Avian influenza virus (AIV) poses a significant threat to poultry and human health globally.
- * Previous research indicated microRNAs (miRNAs) are crucial in host responses to AIV in layer chickens.
- * The role of genetic background in miRNA-mediated AIV response in chickens remains to be fully elucidated.
Purpose of the Study:
- * To investigate the influence of genetic background on miRNA regulation during AIV infection in chickens.
- * To compare miRNA expression patterns in broiler chickens with AIV infection against those in layer chickens.
- * To identify potential molecular mechanisms of host response to AIV by integrating miRNA and mRNA expression profiling.
Main Methods:
- * Deep sequencing of miRNAs and microarray analysis of mRNAs from lung tissues of non-infected and AIV-infected broiler chickens.
- * Isolation of total RNA and subsequent high-throughput sequencing and gene expression profiling.
- * Bioinformatic analysis to identify differentially expressed miRNAs and mRNAs.
Main Results:
- * Deep sequencing identified 271 known and 1 novel miRNA, with 121 differentially expressed in AIV-infected broiler lungs.
- * AIV infection led to higher expression of most miRNAs in broiler lungs, contrasting with findings in layer chickens.
- * Microarray analysis revealed 508 differentially expressed mRNAs, with 347 down-regulated, following AIV infection.
Conclusions:
- * Specific miRNAs (gga-miR-34a, 146a, 155, etc.) and genes (MX1, IL-8, IRF-7, etc.) are identified as key regulators of AIV host response in broiler lungs.
- * The distinct miRNA expression patterns suggest a different regulatory mechanism in broilers compared to layers.
- * Further functional studies, such as miRNA or gene knock-down assays, are necessary to confirm these findings and elucidate the underlying mechanisms.
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