Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China.
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.
Dev Comp Immunol. 2021 Aug;121:104101. doi: 10.1016/j.dci.2021.104101. Epub 2021 Apr 16.
The cGAS-STING pathway plays essential roles in detecting cytosolic dsDNA and initiating antiviral and antibacterial responses in vertebrates. However, knowledge about its function in antiviral response of invertebrates is very limited. In the present study, a gene encoding a Mab21-containing protein, a cGAS homologue, was identified from a decapod crustacean Litopenaeus vannamei and designated as LvMab21cp. LvMab21cp was mainly distributed in intestine and hepatopancreas, showing similar expression profile with other genes in the cGAS-STING pathway, such as LvSTING and LvIRF. The expression levels of LvMab21cp, LvSTING and LvIRF were up-regulated in intestine and hepatopancreas of shrimp after white spot syndrome virus (WSSV) infection. Knockdown of LvMab21cp by dsRNA-mediated RNA interference could decrease the expression levels of its putative downstream genes, including LvSTING, LvIRF, LvVago4 and LvVago5, and enhance the in vivo propagation of WSSV in shrimp. Overexpression of LvMab21cp and LvSTING in HEK 293T cells activated the expression of mammalian IFNs upon simulation with interferon stimulatory DNA (ISD). These data suggest that LvMab21cp was a cGAS homologue, a member of the shrimp cGAS-STING pathway, and play an important role during WSSV infection. To our knowledge, this is the first report to show the role of the cGAS-STING pathway in the antiviral response of invertebrates, which will provide new insights into the innate immunity of invertebrates.
cGAS-STING 通路在脊椎动物中发挥着检测细胞溶质 dsDNA 和启动抗病毒和抗细菌反应的重要作用。然而，关于其在无脊椎动物抗病毒反应中的功能的知识非常有限。在本研究中，从十足目甲壳动物凡纳滨对虾中鉴定出一种编码含有 Mab21 蛋白的基因，该基因是 cGAS 的同源物，被命名为 LvMab21cp。LvMab21cp 主要分布在肠和肝胰腺中，与 cGAS-STING 通路中的其他基因（如 LvSTING 和 LvIRF）具有相似的表达谱。LvMab21cp、LvSTING 和 LvIRF 的表达水平在虾感染白斑综合征病毒（WSSV）后在肠和肝胰腺中均上调。dsRNA 介导的 RNA 干扰敲低 LvMab21cp 会降低其假定下游基因的表达水平，包括 LvSTING、LvIRF、LvVago4 和 LvVago5，并增强虾体内 WSSV 的复制。LvMab21cp 和 LvSTING 在 HEK 293T 细胞中的过表达在模拟干扰素刺激 DNA（ISD）时会激活哺乳动物 IFNs 的表达。这些数据表明，LvMab21cp 是 cGAS 的同源物，是虾 cGAS-STING 通路的成员，在 WSSV 感染过程中发挥重要作用。据我们所知，这是首次报道 cGAS-STING 通路在无脊椎动物抗病毒反应中的作用，这将为无脊椎动物的先天免疫提供新的见解。
