OPEN ACCESS ARTICLE
Marek’s Disease Virus Infection Induced Mitochondria Changes in Chickens
by Qin Chu 1,2, Yi Ding 2, Wentao Cai 2, Lei Liu 2, Huanmin Zhang 3, and Jiuzhou Song 2
1
Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100094, China
2
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20740, USA
3
USDA, Agriculture Research Service, Avian Disease and Oncology Laboratory, East Lansing, MI 48823, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019,
20(13), 3150;
https://doi.org/10.3390/ijms20133150
Received: 23 May 2019 / Revised: 24 June 2019 / Accepted: 26 June 2019 / Published: 27 June 2019
(This article belongs to the Special Issue
Exploring the Genotype–Phenotype Map: Regulatory Pathways)
Abstract
Mitochondria are crucial cellular organelles in eukaryotes and participate in many cell processes including immune response, growth development, and tumorigenesis. Marek’s disease (MD), caused by an avian alpha-herpesvirus Marek’s disease virus (MDV), is characterized with lymphomas and immunosuppression. In this research, we hypothesize that mitochondria may play roles in response to MDV infection.
To test it, mitochondrial DNA (mtDNA) abundance and gene expression in immune organs were examined in two well-defined and highly inbred lines of chickens, the MD-susceptible line 72 and the MD-resistant line 63. We found that mitochondrial DNA contents decreased significantly at the transformation phase in spleen of the MD-susceptible line 72 birds in contrast to the MD-resistant line 63. The mtDNA-genes and the nucleus-genes relevant to mtDNA maintenance and transcription, however, were significantly up-regulated. Interestingly, we found that POLG2 might play a potential role that led to the imbalance of mtDNA copy number and gene expression alteration. MDV infection induced imbalance of mitochondrial contents and gene expression, demonstrating the indispensability of mitochondria in virus-induced cell transformation and subsequent lymphoma formation, such as MD development in chicken. This is the first report on relationship between virus infection and mitochondria in chicken, which provides important insights into the understanding on pathogenesis and tumorigenesis due to viral infection.
5. Conclusions
In summary, in this study we have investigated the variability of mtDNA copy number and gene expression level in the three lymphoid organs in response to MDV challenge. We found that MDV challenge had little impact on mtDNA contents in chickens of the MD-resistant line, but the mitochondrial DNA abundance and gene expression level were obviously altered at the transformation phase, especially in spleen, in chickens of the MD-susceptible line. MDV infection significantly increased the mitochondrial gene expression in the spleen tissue of the MD-susceptible birds, albeit a significant decrease of the mtDNA copy number was observed. Meanwhile, many of the nuclear genes related to mitochondrial genome maintenance and gene expression were up-regulated except for POLG2, which was conversely up-regulated in the MD-resistant line. The data indicated that the POLG2 gene may be a potential regulator for the conflict between the mtDNA copy number and the gene expression of mitochondria in the MD-susceptible birds, directly resulting in imbalance between metabolic and cell signaling and finally the MD pathogenesis and oncogenesis. Further work is warranted to look into mtDNA replication and gene transcription as well as the mitochondria regulation mechanism in relation with MDV infection in chicken.
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Two different chicken lines, two different mtDNAs, one is MD-resistant while the other is MD-susceptible.
A tropical Palawan chicken will have a different mtDNA to that of a temperate chicken breed.