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.
Highlights
Mitochondria, the well-known cytoplasmic organelles for energy making in eukaryotic cells, play important roles in many cell processes, such as small molecules metabolism [1], ion homeostasis [2], immune response [3,4], cell proliferation, and apoptosis [5,6]
It was reported that herpes simplex virus type 1 (HSV-1) and HSV-2 in human trigger mtDNA damage or loss following by mitochondrial dysfunction and the depleting of mRNA encoded by the mitochondrial genomes [15,27]
In this study we have investigated the variability of mtDNA copy number and gene expression level in the three lymphoid organs in response to Marek’s disease virus (MDV) challenge
Summary
Mitochondria, the well-known cytoplasmic organelles for energy making in eukaryotic cells, play important roles in many cell processes, such as small molecules metabolism [1], ion homeostasis [2], immune response [3,4], cell proliferation, and apoptosis [5,6]. Mitochondrion is very special because it contains its own genome (mtDNA), which is a circular molecule and encodes a total of 13 proteins that are all core components of oxidative phosphorylation. There may be hundreds of mitochondria in one cell and one mitochondrion may have multiple copies of mtDNA. It is speculated that the copy number of mtDNA plays a part in mitochondrial biogenesis and regulates mitochondrial functions. Diploid cells may contain a range of 1–10,000 mtDNA molecules depending on cell types and can change over time, where cells with greater energy needs usually have more mitochondria or mtDNA than cells with less needs [7,8]. The change in mtDNA contents is reported to be a useful clinical biomarker for disease diagnose [9,10]
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