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Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus.

ABSTRACT: Newcastle disease virus (NDV) has a devastating impact on poultry production in developing countries. This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV susceptibility after challenge with a high-titer inoculum of lentogenic NDV. The Fayoumi line had a significantly lower NDV load postchallenge than the Leghorn line, demonstrating the Fayoumi line's classification as a relatively NDV-resistant breed. Examination of the trachea transcriptome showed a large increase in immune cell infiltration in the trachea in both lines at all times postinfection. The pathways conserved across lines and at all three time points postinfection included iCOS-iCOSL signaling in T helper cells, NF-?B signaling, the role of nuclear factor of activated T cells in the regulation of the immune response, calcium-induced T lymphocyte apoptosis, phospholipase C signaling, and CD28 signaling in T helper cells. Although shared pathways were seen in the Fayoumi and Leghorn lines, each line showed unique responses as well. The downregulation of collagen and the activation of eukaryotic translation initiation factor 2 signaling in the Fayoumis relative to the Leghorns at 2 days postinfection may contribute to the resistance phenotype seen in the Fayoumis. This study provides a further understanding of host-pathogen interactions which could improve vaccine efficacy and, in combination with genome-wide association studies, has the potential to advance strategies for breeding chickens with enhanced resistance to NDV.

SUBMITTER: Deist MS

PROVIDER: S-EPMC5424241 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus.

Deist Melissa S MS Gallardo Rodrigo A RA Bunn David A DA Kelly Terra R TR Dekkers Jack C M JCM Zhou Huaijun H Lamont Susan J SJ

Clinical and vaccine immunology : CVI 20170505 5

Newcastle disease virus (NDV) has a devastating impact on poultry production in developing countries. This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV susceptibility after challenge with a high-titer inoculum of lentogenic NDV. The Fayoumi line had a significantly lower NDV load postchallenge than the Leghorn line, demonstrating the Fayoumi line's classification as a relatively NDV-resistant breed. Examination of the trachea tran ...[more]

PMID: 28331077

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Project description:BackgroundNewcastle disease virus (NDV) is a threat to poultry production worldwide. A better understanding of mechanisms of resistance and susceptibility to this virus will improve measures for NDV prevention and control. Males and females from resistant Fayoumi and susceptible Leghorn lines were either challenged with a lentogenic strain of the virus or given a mock infection at 3 weeks of age. The lung transcriptomes generated by RNA-seq were studied using contrasts across the challenged and nonchallenged birds, the two lines, and three time points post-infection, and by using Weighted Gene Co-expression Network Analysis (WGNCA).ResultsGenetic line and sex had a large impact on the lung transcriptome. When contrasting the challenged and nonchallenged birds, few differentially expressed genes (DEG) were identified within each line at 2, 6, and 10 days post infection (dpi), except for the more resistant Fayoumi line at 10 dpi, for which several pathways were activated and inhibited at this time. The interaction of challenge and line at 10 dpi significantly impacted 131 genes (False Discovery Rate (FDR) <0.05), one of which was PPIB. Many DEG were identified between the Fayoumi and Leghorns. The number of DEG between the two lines in the challenged birds decreased over time, but increased over time in the nonchallenged birds. The nonchallenged Fayoumis at 10 dpi showed enrichment of immune type cells when compared to 2 dpi, suggesting important immune related development at this age. These changes between 10 and 2 dpi were not identified in the challenged Fayoumis. The energy allocated to host defense may have interrupted normal lung development. WGCNA identified important modules and driver genes within those modules that were associated with traits of interest, several of which had no known associated function.ConclusionsThe lines' unique response to NDV offers insights into the potential means of their resistance and susceptibility. The lung transcriptome shows a unique response to lentogenic NDV compared to a previous study on the trachea of the same birds. It is important to analyze multiple tissues in order to best understand the chicken's overall response to NDV challenge and improve strategies to combat this devastating disease.

Project description:Heat stress results in reduced productivity, anorexia, and mortality in chickens. The objective of the study was to identify genes and signal pathways associated with heat stress and Newcastle disease virus (NDV) infection in the liver of chickens through RNA-seq analysis, using two highly inbred chicken lines (Leghorn and Fayoumi). All birds were held in the same environment until 14 days of age. On day 14, half the birds were exposed to 38 °C with 50% relative humidity for 4 h, then 35 °C until the end of the experiment. The remaining birds were kept at 25 °C throughout the experiment. The heat-treated birds were inoculated at 21 days of age with 107 EID50 (One EID50 unit is the amount of virus that will infect 50 percent of inoculated embryos) NDV La Sota strain to investigate the effects of both heat stress and NDV infection. Physiological parameters were recorded as blood phenotypes at three stages: acute heat (AH), chronic heat (CH1), and chronic heat combined with NDV infection (CH&NDV), at 4 h, 7 days, and 10 days post-initiation of heat treatment, respectively. Our previous work revealed that the heat-resilient Fayoumi line maintained a more stable acid-base balance in their blood compared to the Leghorn line. Liver samples were harvested on both AH and CH&NDV to characterize the transcriptome profiles of these two inbred lines. Both genetic lines and treatments had large impact on the liver transcriptome. Fayoumi birds had more differentially expressed genes (DEGs) than Leghorn birds for both treatments. Metabolic and immune-related genes were on the DEG list, with Fayoumi having more immune-related DEGs than Leghorns, which was confirmed by gene functional enrichment analysis. Weighted correlation network analysis (WGCNA) indicated that the driver genes such as Solute Carrier Family genes could be very important for stabilizing the acid-base balance in Fayoumi birds during heat stress. Therefore, candidate genes such solute carrier family genes could be potential genetic targets that are regulated by Fayoumis to maintain physical hemostasis under heat stress. Differential gene expression showed that Leghorns mainly performed metabolic regulation in response to heat stress and NDV infection, while Fayoumis regulated both immune and metabolic functions. This study provides novel insights and enhances our understandings of liver response to heat stress of heat resilient and susceptible inbred chicken lines.

Dataset Information

Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus.

Publications

Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus.

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