Makino Shizuka, Hamajima Rina, Saito Aya, Tomizaki Moe, Iwamoto Asako, Kobayashi Michihiro, Yamada Hayato, Ikeda Motoko
Laboratory of Sericulture and Entomoresources, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Laboratory of Sericulture and Entomoresources, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Dev Comp Immunol. 2018 Jul;84:133-141. doi: 10.1016/j.dci.2018.02.009. Epub 2018 Feb 12.
Apoptosis is important in antiviral immunity and affects viral multiplication and pathogenesis. Here, we showed that Bombyx mori cells transiently expressing B. mori homolog of the tumor suppressor p53 (Bm-p53) protein underwent apoptosis accompanied by elevated caspase-3-like protease activity and processing of B. mori Dronc (Bm-Dronc). RNAi-mediated silencing of bm-p53 expression, which significantly diminished accumulation of bm-p53 transcript and Bm-p53 protein, prevented apoptosis of B. mori cells infected with a recombinant B. mori nucleopolyhedrovirus defective in the anti-apoptotic p35 gene (vBmΔp35) and abolished the activation of caspase-3-like protease and processing of Bm-Dronc. Apoptosis in vBmΔp35-infected B. mori cells is associated with viral DNA replication, suggesting involvement of the DNA damage response. The Bm-p53 pro-apoptotic function is also found in Spodoptera frugiperda and Lymantria dispar cells. These results indicate that apoptosis induction in vBmΔp35-infected B. mori cells is a Bm-p53-mediated process promoted by the commencement of viral DNA replication.
细胞凋亡在抗病毒免疫中很重要，并且影响病毒的增殖和发病机制。在此，我们表明瞬时表达肿瘤抑制因子p53的家蚕同源物（Bm-p53）蛋白的家蚕细胞会发生细胞凋亡，同时伴有类半胱天冬酶-3蛋白酶活性升高以及家蚕Dronc（Bm-Dronc）的加工处理。RNA干扰介导的bm-p53表达沉默显著减少了bm-p53转录本和Bm-p53蛋白的积累，从而阻止了感染抗凋亡p35基因缺陷的重组家蚕核型多角体病毒（vBmΔp35）的家蚕细胞发生凋亡，并消除了类半胱天冬酶-3蛋白酶的激活以及Bm-Dronc的加工处理。vBmΔp35感染的家蚕细胞中的细胞凋亡与病毒DNA复制相关，提示DNA损伤反应的参与。在草地贪夜蛾和舞毒蛾细胞中也发现了Bm-p53的促凋亡功能。这些结果表明，vBmΔp35感染的家蚕细胞中的细胞凋亡诱导是一个由病毒DNA复制启动促进的Bm-p53介导的过程。
