Induction of Porcine Dermatitis and Nephropathy Syndrome in Piglets by Infection with Porcine Circovirus Type 3
Induction of Porcine Dermatitis and Nephropathy Syndrome in Piglets by Infection with Porcine Circovirus Type 3
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DOI：
10.1128/jvi.02045-18
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发表时间：
2019-02-01
影响因子：
5.4
通讯作者：
Liu, Jue
中科院分区：
文献类型：
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作者：
Jiang, Haijun;Wang, Dan;Liu, Jue
猪圆环病毒3型(PCV3)是一种新发现的猪圆环病毒，与猪皮炎和肾病综合征(PDNS)样临床症状、繁殖障碍、心脏病理以及仔猪和母猪的多系统炎症有关。然而，PCV3感染生物学和发病机制的许多方面仍不清楚。在这里，我们使用从PCV3感染性DNA克隆中拯救出来的PCV3病毒库经鼻接种4周龄和8周龄的无特定病原体的仔猪，以评估PCV3的致病机理。对于4周龄仔猪，单独接种PCV3或PCV3联合锁孔帽状血蓝蛋白免疫刺激后，均可观察到典型的类似PDNS的临床症状，接种后28d的死亡率均为40%(2/5)。两种类型的接种仔猪在血清中的病毒载量呈现类似的进行性增加，并在接种后血清转换为PCV3衣壳抗体。在两种接种仔猪的肺、心、肾、淋巴结、脾、肝和小肠等组织器官中均检测到病理损伤和PCV3特异性抗原。IL-1β、IL-6、IL-23α、γ-干扰素、肿瘤坏死因子-α和趋化因子配体5等促炎细胞因子和趋化因子水平在两组仔猪均显著升高。8周龄仔猪接种PCV3后也表现出类似PDNS样疾病，但没有死亡，各种组织和器官的病理损害和PCV3抗原证明了这一点。这些结果首次表明，猪圆环病毒3型是一种新出现的猪圆环病毒，可引起猪的皮炎和肾病综合征(PDNS)样的临床症状和其他全身性疾病。为了探讨PCV3感染的体内致病机制，我们用从PCV3感染性DNA克隆中回收的PCV3病毒株经鼻接种4周龄和8周龄的无特定病原体的仔猪，并证明了单独接种PCV3或PCV3与锁孔帽状血蓝蛋白免疫刺激联合接种的动物成功复制了PDNS样疾病。接种PCV3的4周龄和8周龄的仔猪在血清中的病毒载量都有类似的增加，并已血清转换为PCV3衣壳抗体。PCV3免疫后各组织器官均可检测到病理损害和PCV3特异性抗原，而血清中大量的促炎细胞因子和趋化因子显著上调。这些结果将为研究PCV3在仔猪中的致病机制提供重要信息。
Porcine circovirus type 3 (PCV3) is an emerging porcine circovirus that has been associated with porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, reproductive failure, cardiac pathologies, and multisystemic inflammation in piglets and sows. Many aspects of PCV3 infection biology and pathogenesis, however, remain unknown. Here, we used a PCV3 virus stock from the rescue of an infectious PCV3 DNA clone to intranasally inoculate 4- and 8-week-old specificpathogen-free piglets for evaluation of PCV3 pathogenesis. For 4-week-old piglets, typical clinical signs resembling those of PDNS-like disease were observed when piglets were inoculated with PCV3 alone or PCV3 combined with immunostimulation by keyhole limpet hemocyanin, with a mortality of 40% (2/5) for both types of inoculated piglets during a 28-day observation period postinoculation. Both types of inoculated piglets showed similar progressive increases in viral loads in the sera and had seroconverted to PCV3 capsid antibody after inoculation. Pathological lesions and PCV3-specific antigen were detected in various tissues and organs, including the lung, heart, kidney, lymph nodes, spleen, liver, and small intestine, in both types of inoculated piglets. The levels of proinflammatory cytokines and chemokines, including interleukin 1 beta (IL-1 beta), IL-6, IL-23 alpha, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and chemokine ligand 5 (CCL5), were significantly upregulated in both groups of inoculated piglets. Eight-week-old piglets also exhibited a similar PDNS-like disease but without death after PCV3 inoculation, as evidenced by pathological lesions and PCV3 antigen in various tissues and organs. These results show for the first time successful reproduction of PDNS-like disease by PCV3 infection and further provide significant information regarding the pathogenesis of PCV3 in piglets.IMPORTANCE Porcine circovirus type 3 (PCV3), an emerging porcine circovirus, is considered the cause of porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs and other systemic diseases in piglets and sows. To evaluate the pathogenesis of PCV3 infection in vivo, we used a PCV3 virus stock from the rescue of an infectious PCV3 DNA clone to intranasally inoculate 4- and 8-week-old specific-pathogen-free piglets and demonstrated successful reproduction of PDNS-like disease in animals that were inoculated with PCV3 alone or PCV3 combined with immunostimulation by keyhole limpet hemocyanin. Both 4- and 8-week-old PCV3-inoculated piglets showed similar increases in viral loads in the sera and had seroconverted to PCV3 capsid antibody. Pathological lesions and PCV3-specific antigen were detected in various tissues and organs, while numerous proinflammatory cytokines and chemokines in the sera were significantly upregulated after PCV3 inoculation. These results will provide significant information regarding the pathogenesis of PCV3 in piglets.