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

作者：Lin Ping Yuan; Liu Hung Jen; Chang Ching Dong; Chang Chi I; Hsu Jue Liang; Liao Ming Huei; Lee Jeng Woei; Shih Wen Ling^*

来源：Archives of Virology, 2011, 156(11): 1917-1929.

DOI：10.1007/s00705-011-1063-3

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 sigma C overexpression. The analysis indicated that in the set of DNA-damage-responsive genes, DDIT-3 and GADD45 alpha were both upregulated by viral infection and sigma C 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 sigma C caused apoptosis mediated by DNA damage signaling. ROS scavenger NAC, caffeine and an ATM-specific inhibitor significantly reduced ARV S1133- and sigma C-induced DNA breaks, DDIT-3 and GADD45 alpha expression, H2AX phosphorylation, and apoptosis. Overexpression of DDIT-3 and GADD45 alpha enhanced the oxidative stress and apoptosis induced by ARV S1133 and sigma C. In conclusion, our results demonstrate the involvement of the DNA-damage-signaling pathway in ARV S1133- and sigma C-induced apoptosis.

• 出版日期2011-11