College of Animal Science and Veterinary Medicine, Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China.
Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Tai'an, China.
Front Immunol. 2018 Jan 25;9:49. doi: 10.3389/fimmu.2018.00049. eCollection 2018.
Hydropericardium syndrome and inclusion body hepatitis, together called hydropericardium-hepatitis syndrome, are acute infectious diseases found in chickens. These diseases are caused primarily by fowl adenovirus serotype 4 (FAdV-4) strains. In this study, we isolated a FAdV-4 strain (SD0828) from clinically diseased chickens and phylogenetically analyzed the L1 loops of the hexon protein sequences in 3-week-old specific pathogen-free chickens and ducks infected intramuscularly and orally, determining differences in the pathogenicity by observing clinical signs and gross and histological lesions. We also detected the viral load in tissue samples. Postinfection necropsy showed that all chickens but no ducks exhibited typical necropsy lesions. Additionally, all chickens infected intramuscularly died within 2 days postinfection (dpi), and all those infected orally died within 5 dpi, whereas no infected ducks died before 28 dpi. Quantitative real-time polymerase chain reaction analysis was used to determine the viral load in the tissues of hearts, livers, spleens, lungs, and kidneys and in cloacal cotton swabs from infected chickens and ducks at 1, 2, 3, 5, 7, 14, 21, and 28 dpi. The greatest number of viral DNA copies was found in the livers of infected chickens, yet no virus was found in any samples from infected ducks. In addition, the viral load increased over time in both chicken and duck embryo fibroblasts (CEFs and DEFs, respectively); in the former, replication speed was significantly greater than in the latter. Innate immune responses were also studied, both and . In CEFs, DEFs, and chickens infected intramuscularly, but not in infected ducks, mRNA expression levels of proinflammatory cytokines (interleukin-6 and -8) and interferon-stimulated genes (Mx and OAS) were significantly upregulated. Although some cytokines showed significant upregulation in the oral chickens, most did not change significantly. Finally, the duck retinoic acid-inducible gene I and its caspase activation and recruitment domain both had significant antiviral functions in CEFs, particularly after 24 h postinfection. Taken together, this research provides new insights into the interactions between FAdV-4 and the innate immune systems of studied hosts (chickens and ducks).
心包积液综合征和包涵体肝炎,统称为心包积液-肝炎综合征,是在鸡中发现的急性传染病。这些疾病主要由禽腺病毒血清型 4(FAdV-4)株引起。在这项研究中,我们从临床患病鸡中分离出一株 FAdV-4 株(SD0828),并对 3 周龄 SPF 鸡和鸭经肌肉和口服感染后六邻体蛋白 L1 环序列进行了系统进化分析,通过观察临床症状和大体及组织学病变来确定致病性差异。我们还检测了组织样本中的病毒载量。感染后剖检显示,所有鸡都出现了典型的剖检病变,但鸭没有。此外,所有肌肉感染的鸡在感染后 2 天内死亡,所有口服感染的鸡在感染后 5 天内死亡,而感染的鸭在 28 天前没有死亡。定量实时聚合酶链反应分析用于确定感染鸡和鸭的心、肝、脾、肺和肾组织以及感染后 1、2、3、5、7、14、21 和 28 天的泄殖腔棉拭子中的病毒载量。在感染鸡的肝脏中发现了最多的病毒 DNA 拷贝,但在任何感染鸭的样本中都没有发现病毒。此外,病毒载量在鸡和鸭胚胎成纤维细胞(CEF 和 DEF)中随时间推移而增加;在前者中,复制速度明显快于后者。还研究了固有免疫反应,包括 和 。在 CEF、DEF 和肌肉感染的鸡中,但在感染的鸭中,促炎细胞因子(白细胞介素-6 和 -8)和干扰素刺激基因(Mx 和 OAS)的 mRNA 表达水平显著上调。虽然一些细胞因子在口服鸡中表达显著上调,但大多数没有显著变化。最后,鸭视黄酸诱导基因 I 及其半胱氨酸天冬氨酸蛋白酶激活和募集结构域在 CEF 中均具有显著的抗病毒功能,特别是在感染后 24 小时。综上所述,这项研究为 FAdV-4 与研究宿主(鸡和鸭)固有免疫系统之间的相互作用提供了新的见解。