Jiangsu Key Laboratory of Sericultural Biology and Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, 212100, China; Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang, 212100, China.
Dev Comp Immunol. 2023 Sep;146:104736. doi: 10.1016/j.dci.2023.104736. Epub 2023 May 18.
BmTsp.A (Bombyx mori Tetraspanin A) is one of the four transmembrane proteins which are capable to regulate multiple aspects of the immune response and are involved in various stages of viral invasion of the hosts. This study focused on the sequence features, analysis of expression pattern, as well as the effect of BmTsp.A on BmNPV (Bombyx mori nucleopolyhedrovirus) infection in the apoptotic pathway. BmTsp.A features the typical tetraspanins family, including four transmembrane domains and a major large extracellular loop domain. It is highly expressed specifically in the malpighian tubes, and its expression is increased by BmNPV induction for 48 h and 72 h. Overexpression and RNAi (RNA interference) mediated by siRNA reveal that BmTsp.A can promote the infection and replication of the virus. In addition, the overexpression of BmTsp.A regulates BmNPV-induced apoptosis, leading to changes in the expression of apoptosis-related genes and thus affecting viral proliferation. When subjected to stimulation by BmNPV infection, on the one hand, BmTsp.A inhibits Bmp53 through a Caspase-dependent pathway, which consequently promotes the expression of Bmbuffy, thereby activating BmICE to inhibit apoptosis and causing the promotion of viral proliferation. On the other hand, BmTsp.A inhibits the expression of BmPTEN and BmPkc through the phosphatidylinositol 3 kinase (PI3K)/protein kinaseB(AKT) signaling pathway, thus affecting the regulation of apoptosis. To summarize, our results demonstrate that BmTsp.A promotes viral infection and replication by inhibiting apoptosis, which is fundamental for understanding the pathogenesis of BmNPV and the immune defense mechanism of silkworm.
BmTsp.A（家蚕四跨膜蛋白 A）是能够调节免疫反应多个方面的四个跨膜蛋白之一，参与宿主病毒入侵的各个阶段。本研究重点研究了 BmTsp.A 的序列特征、表达模式分析以及在凋亡途径中对 BmNPV（家蚕核型多角体病毒）感染的影响。BmTsp.A 具有典型的四跨膜蛋白家族特征，包括四个跨膜结构域和一个主要的大细胞外环结构域。它在马氏管中特异性高表达，其表达在 BmNPV 诱导后 48 h 和 72 h 增加。通过 siRNA 介导的过表达和 RNAi（RNA 干扰）揭示，BmTsp.A 可以促进病毒的感染和复制。此外，BmTsp.A 的过表达调节 BmNPV 诱导的细胞凋亡，导致凋亡相关基因的表达变化，从而影响病毒的增殖。当受到 BmNPV 感染的刺激时，一方面，BmTsp.A 通过 Caspase 依赖性途径抑制 Bmp53，从而促进 Bmbuffy 的表达，激活 BmICE 抑制凋亡，促进病毒增殖。另一方面，BmTsp.A 通过磷脂酰肌醇 3 激酶（PI3K）/蛋白激酶 B（AKT）信号通路抑制 BmPTEN 和 BmPkc 的表达，从而影响凋亡的调节。总之，我们的研究结果表明，BmTsp.A 通过抑制凋亡来促进病毒的感染和复制，这对于理解 BmNPV 的发病机制和家蚕的免疫防御机制至关重要。
