PDF(Pubmed)
Abstract：
Marek\'s disease virus (MDV) is an economic concern for the poultry industry due to its poorly understood pathophysiology. Purinergic receptors (PRs) are potential therapeutic targets for viral infections, including herpesviruses, prompting our investigation into their role in MDV pathogenesis. The current study is part of an experimental series analyzing the expression of PRs during MDV infection. To address the early or short-acting P2 PR responses during natural MDV infection, we performed an \"exposure\" experiment where age-matched chickens were exposed to experimentally infected shedders to initiate natural infection. In addition, select non-PR regulatory gene responses were measured. Two groups of naïve contact chickens (n = 5/breed/time point) from MD-resistant (White Leghorns: WL) and -susceptible (Pure Columbian) chicken lines were housed separately with experimentally infected PC (×PC) and WL (×WL) chickens for 6 or 24 h. Whole lung lavage cells (WLLC) were collected, RNA was extracted, and RT-qPCR assays were used to measure specific PR responses. In addition, other potentially important markers in pathophysiology were measured. Our study revealed that WL chickens exhibited higher P1 PR expression during natural infection. WL chickens also showed higher expression of P1A3 and P2X3 at 6 and 24 h when exposed to PC-infected chickens. P2X5 and P2Y1 showed higher expression at 6 h, while P2Y5 showed higher expression at 6 and 24 h; regardless of the chicken line, PC chickens exhibited higher expression of P2X2, P2Y8, P2Y10, P2Y13, and P2Y14 when exposed to either group of infected chickens. In addition, MDV infection altered the expression of DDX5 in both WL and PC groups exposed to PC-infected birds only. However, irrespective of the source of exposure, BCL2 and ANGPTL4 showed higher expression in both WL and PC. The expression of STAT1A and STAT5A was influenced by time and breed, with major changes observed in STAT5A. CAT and SOD1 expression significantly increased in both WL and PC birds, regardless of the source of infection. GPX1 and GPX2 expression also increased in both WL and PC, although overall lower expression was observed in PC chickens at 24 h compared to 6 h. Our data suggest systemic changes in the host during early infection, indicated by the altered expression of PRs, DDX5, BCL2, ANGPTL4, and other regulatory genes during early MDV infection. The relative expression of these responses in PC and WL chickens suggests they may play a key role in their response to natural MDV infection in the lungs and long-term pathogenesis and survival.
摘要：
马立克氏病病毒（MDV）由于其病理生理学知之甚少，因此是家禽业的经济问题。嘌呤能受体（PRs）是病毒感染的潜在治疗靶点，包括疱疹病毒,促使我们研究它们在MDV发病机制中的作用。本研究是分析MDV感染期间PRs表达的实验系列的一部分。为了解决自然MDV感染期间的早期或短效P2PR反应，我们进行了“暴露”实验，其中年龄匹配的鸡暴露于实验感染的脱落体以引发自然感染。此外,选择非PR调节基因反应进行测量。将来自MD抗性（白色Leghorns：WL）和易感（纯哥伦布）鸡品系的两组未接触鸡（n=5/品种/时间点）分别与实验感染的PC（×PC）和WL（×WL）鸡饲养6或24小时。收集全肺灌洗细胞（WLLC），提取RNA,和RT-qPCR测定用于测量特异性PR应答。此外,检测了病理生理学中其他潜在的重要标志物.我们的研究表明，WL鸡在自然感染期间表现出更高的P1PR表达。当暴露于PC感染的鸡时，WL鸡在6和24小时也显示出P1A3和P2X3的较高表达。P2X5和P2Y1在6h时显示出较高的表达，而P2Y5在6和24小时显示出较高的表达；无论鸡系，当暴露于两组感染的鸡中时，PC鸡表现出更高的P2X2，P2Y8，P2Y10，P2Y13和P2Y14表达。此外,MDV感染改变了仅暴露于PC感染的鸟类的WL和PC组中DDX5的表达。然而,不管暴露的来源，BCL2和ANGPTL4在WL和PC中均显示出较高的表达。STAT1A和STAT5A的表达受时间和品种的影响,在STAT5A中观察到重大变化。CAT和SOD1表达在WL和PC鸟类中显著增加，不管感染源。GPX1和GPX2在WL和PC中的表达也增加，尽管与6小时相比，在24小时的PC鸡中观察到总体较低的表达。我们的数据表明在早期感染期间宿主的系统性变化，由PR的表达改变表明，MDV感染早期的DDX5、BCL2、ANGPTL4和其他调控基因。这些反应在PC和WL鸡中的相对表达表明，它们可能在其对肺部自然MDV感染的反应以及长期发病机理和存活中起关键作用。
