Location: Endemic Poultry Viral Diseases ResearchTitle: 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 - Oak Ridge Institute For Science And Education (ORISE)|
|CHANG, SHUANG - Shangdong Agricultural University|
|XIE, QINGMEI - South China Agricultural University|
|ZHAO, PENG - Shangdong Agricultural University|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/11/2019
Publication Date: 10/2/2019
Citation: Dong, K., Chang, S., Xie, Q., Zhao, P., Zhang, H. 2019. RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv+MDV in chickens. Scientific Reports. 9:14182. https://doi.org/10.1038/s41598-019-50561-x.
Interpretive Summary: Marek’s disease (MD) is one of avian tumor virus-induced diseases of chickens and continues posing a real threat to the world poultry industry economically. Genetic resistance to MD certainly augments current control measures of the disease but, so far, it has been playing a far from sufficiently role due to lack of adequate information on the mechanisms underline genetic resistance to MD. Using a cutting-edge technology in genomics study, two highly inbred lines of chickens were examined for what genes were different in expression in response to MD virus (MDV) challenge. Data from this study showed dozens of genes involved in host defense system reacted differently in response to MDV challenge. It is anticipated that these findings will facilitate advancement in the fundamental understanding on mechanisms of genetic resistance to MD.
Technical Abstract: Very virulent plus Marek’s disease (MD) virus (vv+MDV) induces tumors in relatively resistant lines of chickens and high 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 an inbred chicken line (line 63) relatively resistant to MD and another inbred line (line 72) highly susceptible to MD with a vv+MDV, and performed RNA-sequencing analysis 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 were identified in response to a vv+MDV challenge during the period of latency phase in the resistant and susceptible lines of chickens, respectively. Furthermore, direct comparisons between samples of the two lines of chickens identified 90 and 126 differentially expressed genes for the control and MDV challenged groups, respectively. The differentially expressed gene profiles illustrated that intensive defense responses were significantly induced by MDV at 10 dpi and also at 21 dpi but with slight changes in the resistant line. In contrast, vv+MDV induced a measurable suppression of host gene expression 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 provided a piece of indirect evidence that time point for MDV reactivation differs between the genetic lines of chickens with different genetic resistance to MD. Early MDV reactivation might be necessary and potent to host defense system readiness for damage control in disease progression, which consequently result in measurable differences in phenotypic characteristics including early mortality (8 to 20 dpi) tumor incidence between the resistant and susceptible lines of chickens. Combining differential gene expression patterns with reported function terms and quantitative trait loci, a total of top 27 genes was identified 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 shed insights on the tumor virus-induced tumorigenesis in general, and demonstrated that this kind of MD study may serve as a model for oncology study involved with tumor viruses.