Lu Zhihua, Li Haiqin, Gao Xiaona, Fu Duanfeng, Huang Haoyu, Huang Cheng, Wu Meiqin, Guo Xiaoquan
Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.
Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China; Institute of Animal Husbandry and Veterinary Medicine, Jiangxi Academy of Agricultural Sciences, Nanchang, Jiangxi 330200, China.
Poult Sci. 2025 Jan;104(1):104600. doi: 10.1016/j.psj.2024.104600. Epub 2024 Nov 27.
The ongoing Goose astrovirus (GoAstV) epidemic, which primarily infects goslings causing severe liver damage, has inflicted considerable damage on the poultry industry. Endoplasmic reticulum stress (ERS) is a significant modulator of several viral infections, while severe ERS may result in apoptosis. This study examined the roles and possible mechanisms of ERS and apoptosis in GoAstV-induced liver injury in goslings. Two hundred Xingguo gray geese were chosen and randomly separated into two groups (Con and Dis). The Dis group received a subcutaneous injection of GoAstV genotype 2 (GoAstV-2) JX01 (2 × 10 TCID/0.2 mL), whereas the Con group received a subcutaneous injection of 0.2 mL physiological saline, both at 1 day of life. Subsequent analyses demonstrate that the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased following GoAstV infection. Hematoxylin and eosin (HE) staining revealed swollen and ruptured hepatocytes, with significant inflammatory cell infiltration. Electron microscopy revealed expansion of the endoplasmic reticulum (ER) and aggregation of chromatin at the periphery. TUNEL testing further demonstrated an increase in the quantity of positive cells. RT-qPCR and Western blot analyses indicated that GoAstV infection enhanced the expression of ER Ca release channels (IP3R and RYR) and calmodulin-dependent protein kinase II (CaMKII), while decreasing the expression of ER Ca uptake channels (SERCA). Further, GoAstV infection activated ERS-related factors, including GRP78, IRE1α, PERK, ATF6, eIF2α, ATF4, CHOP, TRAF2, and JNK, induced the expression of pro-apoptotic factors (Caspase-3, Caspase-9, and Bax), and inhibited the mRNA and protein expression of the anti-apoptotic factor Bcl-2. Correlation analysis further revealed a potential relationship among ERS gene expression, apoptotic gene expression, and liver injury. In summary, GoAstV infection can lead to liver injury by interfering with ER Ca homeostasis, exacerbating ERS and inducing hepatocyte apoptosis.
正在流行的鹅星状病毒（GoAstV）疫情主要感染雏鹅，导致严重的肝脏损伤，给家禽业造成了相当大的损失。内质网应激（ERS）是几种病毒感染的重要调节因子，而严重的ERS可能导致细胞凋亡。本研究探讨了ERS和细胞凋亡在GoAstV诱导的雏鹅肝损伤中的作用及可能机制。选取200只兴国灰鹅，随机分为两组（对照组和疾病组）。疾病组在雏鹅1日龄时皮下注射2型GoAstV（GoAstV-2）JX01（2×10 TCID/0.2 mL），而对照组皮下注射0.2 mL生理盐水。后续分析表明，GoAstV感染后天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平升高。苏木精-伊红（HE）染色显示肝细胞肿胀、破裂，有明显的炎性细胞浸润。电子显微镜显示内质网（ER）扩张，染色质在外周聚集。TUNEL检测进一步表明阳性细胞数量增加。RT-qPCR和蛋白质免疫印迹分析表明，GoAstV感染增强了内质网钙释放通道（IP3R和RYR）和钙调蛋白依赖性蛋白激酶II（CaMKII）的表达，同时降低了内质网钙摄取通道（SERCA）的表达。此外，GoAstV感染激活了ERS相关因子，包括GRP78、IRE1α、PERK、ATF6、eIF2α、ATF4、CHOP、TRAF2和JNK，诱导了促凋亡因子（Caspase-3、Caspase-9和Bax）的表达，并抑制了抗凋亡因子Bcl-2的mRNA和蛋白质表达。相关性分析进一步揭示了ERS基因表达、凋亡基因表达和肝损伤之间的潜在关系。综上所述，GoAstV感染可通过干扰内质网钙稳态、加剧ERS和诱导肝细胞凋亡导致肝损伤。
