College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, China.
Waterfowl Healthy Breeding Engineering Research Center of Guangdong, Zhongkai University of Agriculture and Engineering, Guangzhou, China.
Front Cell Infect Microbiol. 2024 Oct 22;14:1452158. doi: 10.3389/fcimb.2024.1452158. eCollection 2024.
Since 2016, a highly lethal visceral gout induced by infection with the novel goose astrovirus (GoAstV) resulted in an ongoing outbreak in goslings in China, with a mortality rate ranging from 10% to 50%, and causing considerable economic losses in the goose industry. However, the pathogenesis of GoAstV and the molecular mechanism by which kidney lesions are induced by GoAstV infection are unclear.
In the present study, a GEK cell infection model for GoAstV was established, and the apoptosis, inflammatory and innate immune responses induced by GoAstV were investigated in GEK cells.
The results shown that the expression of proapoptotic proteins, including Bax, caspase-3, caspase-9 and cytochrome , increased in the infection group; however, the expression of the antiapoptotic protein Bcl-2 decreased, indicating that apoptosis was induced by GoAstV infection in GEK cells. Besides, the activation of the RIG-I/MDA5 pathway and the downstream upregulation of proinflammatory cytokines, including the adapter proteins MAVS, IRF7 and NF-κB and the proinflammatory cytokines IL-6, IL-8 and TNF-α, were detected in GEK cells infected with GoAstV. In addition, GoAstV infection induces the activation of the NLPR3 pathway and further stimulates the increased production of IL-1β. In summary, the present study revealed that GoAstV infection could induce apoptosis and the activation of the RIG-I/MDA5 and NLRP3 pathways in GEK cells, as well as the massive release of proinflammatory cytokines.
These results are helpful for elucidating the molecular mechanism of pathological lesions in the kidney in gout goslings infected with GoAstV and the interaction between GoAstV and the innate immune system of the host.
自 2016 年以来，一种新型鹅星状病毒（GoAstV）感染引起的高致死性内脏痛风在中国鹅雏中持续爆发，死亡率在 10%至 50%之间，给鹅业造成了巨大的经济损失。然而，GoAstV 的发病机制以及 GoAstV 感染诱导肾脏病变的分子机制尚不清楚。
本研究建立了 GoAstV 感染 GEK 细胞的模型，研究了 GoAstV 感染诱导的 GEK 细胞凋亡、炎症和固有免疫反应。
结果表明，感染组中促凋亡蛋白 Bax、caspase-3、caspase-9 和细胞色素 C 的表达增加；而抗凋亡蛋白 Bcl-2 的表达减少，表明 GoAstV 感染诱导了 GEK 细胞凋亡。此外，在感染 GoAstV 的 GEK 细胞中，RIG-I/MDA5 途径被激活，下游促炎细胞因子，包括衔接蛋白 MAVS、IRF7 和 NF-κB 以及促炎细胞因子 IL-6、IL-8 和 TNF-α的表达上调。此外，GoAstV 感染诱导 NLPR3 途径的激活，并进一步刺激 IL-1β的大量产生。综上所述，本研究揭示了 GoAstV 感染可诱导 GEK 细胞凋亡以及 RIG-I/MDA5 和 NLRP3 途径的激活，并导致大量促炎细胞因子的释放。
这些结果有助于阐明感染 GoAstV 的痛风鹅雏肾脏病理损伤的分子机制以及 GoAstV 与宿主固有免疫系统的相互作用。
