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RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv?+?MDV in chickens.

ABSTRACT: Very virulent plus Marek's disease (MD) virus (vv?+?MDV) induces tumors in relatively resistant lines of chickens and early mortality in highly susceptible lines of chickens. The vv?+?MDV also triggers a series of cellular responses in both types of chickens. We challenged birds sampled from a highly inbred chicken line (line 63) that is relatively resistant to MD and from another inbred line (line 72) that is highly susceptible to MD with a vv?+?MDV. RNA-sequencing analysis was performed with samples extracted from spleen tissues taken at 10-day and 21-day post infection (dpi). A total of 64 and 106 differentially expressed genes was identified in response to the vv?+?MDV challenge at latent phase in the resistant and susceptible lines of chickens, respectively. Direct comparisons between samples of the two lines identified 90 and 126 differentially expressed genes for control and MDV challenged groups, respectively. The differentially expressed gene profiles illustrated that intensive defense responses were significantly induced by vv?+?MDV at 10 dpi and 21 dpi but with slight changes in the resistant line. In contrast, vv?+?MDV induced a measurable suppression of gene expression associated with host defense at 10 dpi but followed by an apparent activation of the defense response at 21 dpi in the susceptible line of chickens. The observed difference in gene expression between the two genetic lines of chickens in response to MDV challenge during the latent phase provided a piece of indirect evidence that time points for MDV reactivation differ between the genetic lines of chickens with different levels of genetic resistance to MD. Early MDV reactivation might be necessary and potent to host defense system readiness for damage control of tumorigenesis and disease progression, which consequently results in measurable differences in phenotypic characteristics including early mortality (8 to 20 dpi) and tumor incidence between the resistant and susceptible lines of chickens. Combining differential gene expression patterns with reported GO function terms and quantitative trait loci, a total of 27 top genes was selected as highly promising candidate genes for genetic resistance to MD. These genes are functionally involved with virus process (F13A1 and HSP90AB1), immunity (ABCB1LB, RGS5, C10ORF58, OSF-2, MMP7, CXCL12, GAL1, GAL2, GAL7, HVCN1, PDE4D, IL4I1, PARP9, EOMES, MPEG1, PDK4, CCLI10, K60 and FST), and tumor suppression (ADAMTS2, LXN, ARRDC3, WNT7A, CLDN1 and HPGD). It is anticipated that these findings will facilitate advancement in the fundamental understanding on mechanisms of genetic resistance to MD. In addition, such advancement may also provide insights on tumor virus-induced tumorigenesis in general and help the research community recognize MD study may serve as a good model for oncology study involving tumor viruses.

SUBMITTER: Dong K

PROVIDER: S-EPMC6775254 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv + MDV in chickens.

Dong Kunzhe K Chang Shuang S Xie Qingmei Q Zhao Peng P Zhang Huanmin H

Scientific reports 20191002 1

Very virulent plus Marek's disease (MD) virus (vv + MDV) induces tumors in relatively resistant lines of chickens and early mortality in highly susceptible lines of chickens. The vv + MDV also triggers a series of cellular responses in both types of chickens. We challenged birds sampled from a highly inbred chicken line (line 6<sub>3</sub>) that is relatively resistant to MD and from another inbred line (line 7<sub>2</sub>) that is highly susceptible to MD with a vv + MDV. RNA-sequencing analysi ...[more]

PMID: 31578366

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Project description:The Guangxi Partridge chicken is a well-known chicken breed in southern China with good meat quality, which has been bred as a meat breed to satisfy the increased demand of consumers. Compared with line D whose body weight is maintained at the average of the unselected group, the growth rate and weight of the selected chicken group (line S) increased significantly after breeding for four generations. Herein, transcriptome analysis was performed to identify pivotal genes and signal pathways of selective breeding that contributed to potential mechanisms of growth and development under artificial selection pressure. The average body weight of line S chickens was 1.724 kg at 90 d of age, which showed a significant increase at 90 d of age than line D chickens (1.509 kg), although only the internal organ ratios of lung and kidney changed after standardizing by body weight. The myofiber area and myofiber density of thigh muscles were affected by selection to a greater extent than that of breast muscle. We identified 51, 210, 31, 388, and 100 differentially expressed genes (DEGs) in the hypothalamus, pituitary, breast muscle, thigh muscle, and liver between the two lines, respectively. Several key genes were identified in the hypothalamus-pituitary-muscle axis, such as FST, THSB, PTPRJ, CD36, PITX1, PITX2, AMPD1, PRKAB1, PRKAB2, and related genes for muscle development, which were attached to the cytokine-cytokine receptor interaction signaling pathway, the PPAR signaling pathway, and lipid metabolism. However, signaling molecular pathways and the cell community showed that elevated activity in the liver of line S fowl was mainly involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules, and signal transduction. Collectively, muscle development, lipid metabolism, and several signaling pathways played crucial roles in the improving growth performance of Guangxi Partridge chickens under artificial selection for growth rate. These results support further study of the adaptation of birds under selective pressure.

Project description:BACKGROUND: The processing ability of poultry meat is highly related to its ultimate pH, the latter being mainly determined by the amount of glycogen in the muscle at death. The genetic determinism of glycogen and related meat quality traits has been established in the chicken but the molecular mechanisms involved in variations in these traits remain to be fully described. In this study, Chicken Genome Arrays (20 K) were used to compare muscle gene expression profiles of chickens from Fat (F) and Lean (L) lines that exhibited high and low muscle glycogen content, respectively, and of individuals exhibiting extremely high (G+) or low (G-) muscle glycogen content originating from the F2 cross between the Fat and Lean lines. Real-time RT-PCR was subsequently performed to validate the differential expression of genes either selected from the microarray analysis or whose function in regulating glycogen metabolism was well known. RESULTS: Among the genes found to be expressed in chicken P. major muscle, 197 and 254 transcripts appeared to be differentially expressed on microarrays for the F vs. L and the G+ vs. G- comparisons, respectively. Some involved particularly in lipid and carbohydrate metabolism were selected for further validation studies by real-time RT-PCR. We confirmed that, as in mammals, the down-regulation of CEBPB and RGS2 coincides with a decrease in peripheral adiposity in the chicken, but these genes are also suggested to affect muscle glycogen turnover through their role in the cAMP-dependent signalling pathway. Several other genes were suggested to have roles in the regulation of glycogen storage in chicken muscle. PDK4 may act as a glycogen sensor in muscle, UGDH may compete for glycogen synthesis by using UDP-glucose for glucoronidation, and PRKAB1, PRKAG2, and PHKD may impact on glycogen turnover in muscle, through AMP-activated signalling pathways. CONCLUSIONS: This study is the first stage in the understanding of molecular mechanisms underlying variations in poultry meat quality. Large scale analyses are now required to validate the role of the genes identified and ultimately to find molecular markers that can be used for selection or to optimize rearing practices.

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RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv?+?MDV in chickens.

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RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv + MDV in chickens.

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