Zhang Yunsheng, Ding Dingbang, Li Shaofei, Pan Qiong, Ru Jinlong, Zhao Haonan, Yao Guang, Wei Jie, Wang Shuaiqin, Hou Shuisheng, Wang Xia
Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China.
College of Animal Science and Technology, Northwest A&F University, Yangling 712100 Shaanxi, PR China.
Poult Sci. 2025 Feb;104(2):104798. doi: 10.1016/j.psj.2025.104798. Epub 2025 Jan 9.
DHAV-3 is one of the main causative agents of duck viral hepatitis (DVH), an acute and highly lethal infectious disease in duck industry. However, the understanding of the pathogenesis of this virus in ducklings is limited. To dissect the molecular characteristics associated with pathobiology of ducklings to DHAV-3, we applied single-cell RNA-sequencing approach to profile the transcriptome of 1.4 million cells from 14 livers of DHAV-3 susceptible (S) and resistant (R) ducklings during viral infection and 4 uninfected healthy controls. We found that infected S ducks exhibited the activation of type I and II interferon pathways with elevated expression of interferon-stimulated genes (ISGs) compared to infected R ducks and healthy controls. DHAV-3 promoted proinflammatory phenotype and inhibited the cell apoptosis pathway of Kupffer cells of S ducks. Furthermore, we observed the elevated expression of host factor PLAC8 in S ducks and validated its ability to facilitate the infection of DHAV-3. We identified significant dysregulation of various genes in complement and coagulation cascades in hepatocytes2 exclusive to S ducks, together with over-secretion of ANGPTL4 from endothelial cells in S ducks which is confirmed to promote cellular migration, suggesting etiology of coagulopathic complications in ducks with severe DVH. Collectively, this study provides a rich resource for understanding the inflammatory immune signatures and cell communications underlying the pathogenesis of DHAV-3 infection, which may accelerate the development of better diagnostic methods and strategies for controlling this disease.
鸭甲肝病毒3型（DHAV-3）是鸭病毒性肝炎（DVH）的主要致病因子之一，DVH是一种在养鸭业中具有急性和高致死性的传染病。然而，对于这种病毒在雏鸭体内的发病机制了解有限。为了剖析与雏鸭对DHAV-3病理生物学相关的分子特征，我们应用单细胞RNA测序方法，对14只DHAV-3易感（S）和抗性（R）雏鸭在病毒感染期间的14个肝脏以及4个未感染的健康对照的140万个细胞的转录组进行了分析。我们发现，与感染的R雏鸭和健康对照相比，感染的S雏鸭表现出I型和II型干扰素途径的激活，干扰素刺激基因（ISGs）表达升高。DHAV-3促进了S雏鸭库普弗细胞的促炎表型并抑制了其细胞凋亡途径。此外，我们观察到S雏鸭中宿主因子PLAC8的表达升高，并验证了其促进DHAV-3感染的能力。我们发现S雏鸭肝细胞中补体和凝血级联反应中的各种基因存在显著失调，同时S雏鸭内皮细胞中血管生成素样蛋白4（ANGPTL4）分泌过多，这被证实可促进细胞迁移，提示严重DVH雏鸭发生凝血病并发症的病因。总体而言，本研究为理解DHAV-3感染发病机制背后的炎症免疫特征和细胞通讯提供了丰富资源，这可能会加速更好的诊断方法和控制该疾病策略的开发。
