Birnaviruses Group, The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK.
Department of Pathology and Infectious Diseases, Faculty of Health and Medical Sciences, School of Veterinary Medicine, University of Surrey, Guilford GU2 7AL, UK.
Viruses. 2021 May 18;13(5):933. doi: 10.3390/v13050933.
In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds ( < 0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.
为了更好地理解传染性腔上囊炎病毒（IBDV）感染结果的差异，我们将一种非常强毒（vv）株接种到先前报道死亡率超过 24%的近交系 W 白来航鸡，以及先前报道无死亡率的三个近交系（15I、C.B4 和 0）中。在每个实验组中，一些个体的疾病比其他个体更严重，但根据平均临床评分、有大体病理的鸟类百分比、平均囊病变评分和平均峰值囊病毒滴度，15I 系的鸟类疾病较轻。RNA-Seq 分析显示，与 line 15I 相比，W 系更严重的疾病与炎症相关途径、Rho GTPases 调节细胞骨架、烟碱型乙酰胆碱受体信号和 Wnt 信号在囊中的显著上调有关。与 line 15I 鸟类相比，从未感染的 W 系鸟类分离的初级囊细胞群体中，KUL01+巨噬细胞的比例明显更高（<0.01），并且在体外用 LPS 刺激时，其促炎基因表达的上调速度比 line 15I 鸟类更快。我们假设在 IBDV 感染后，囊细胞中促炎细胞因子反应的快速诱导导致 W 系鸟类比 15I 系鸟类的疾病更严重。
