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Avian reovirus S1133-induced DNA damage signaling and subsequent apoptosis in cultured cells and in chickens

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Abstract

In this study, intracellular signaling in ARV S1133-mediated apoptosis was investigated. A microarray was used to examine the gene expression profiles of cells upon ARV S1133 infection and ARV-encoded pro-apoptotic protein σC overexpression. The analysis indicated that in the set of DNA-damage-responsive genes, DDIT-3 and GADD45α were both upregulated by viral infection and σC overexpression. Further investigation demonstrated that both treatments caused DNA breaks, which increased the expression and/or phosphorylation of DNA damage response proteins. ROS and lipid peroxidation levels were increased, and ARV S1133 and σC caused apoptosis mediated by DNA damage signaling. ROS scavenger NAC, caffeine and an ATM-specific inhibitor significantly reduced ARV S1133- and σC-induced DNA breaks, DDIT-3 and GADD45α expression, H2AX phosphorylation, and apoptosis. Overexpression of DDIT-3 and GADD45α enhanced the oxidative stress and apoptosis induced by ARV S1133 and σC. In conclusion, our results demonstrate the involvement of the DNA-damage-signaling pathway in ARV S1133- and σC-induced apoptosis.

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Acknowledgements

This work was supported by a grant from the National Science Council of Taiwan (NSC 98-2313-B-020-004-MY3). We also thank Sarah Parkin for copy-editing the manuscript.

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Graduate Institute and Department of Life Science, Tzu-Chi University, Hualien, Taiwan

    Ping-Yuan Lin & Jeng-Woei Lee

  2. Institute of Molecular Biology, National Chung-Hsing University, Taichung, Taiwan

    Hung-Jen Liu

  3. Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan

    Ching-Dong Chang & Ming-Huei Liao

  4. Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, 1, Shuefu Rd., Neipu, Pingtung, 91201, Taiwan

    Chi-I Chang, Jue-Liang Hsu & Wen-Ling Shih

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  1. Ping-Yuan Lin
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Correspondence to Wen-Ling Shih.

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Lin, PY., Liu, HJ., Chang, CD. et al. Avian reovirus S1133-induced DNA damage signaling and subsequent apoptosis in cultured cells and in chickens. Arch Virol 156, 1917–1929 (2011). https://doi.org/10.1007/s00705-011-1063-3

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