P247 and p523: two in vivo-expressed megalocytivirus proteins that induce protective immunity and are essential to viral infection.
P247 and p523: two in vivo-expressed megalocytivirus proteins that induce protective immunity and are essential to viral infection.
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DOI：
10.1371/journal.pone.0121282
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Zhang J;Zhang BC;Sun L
巨细胞病毒是一种DNA病毒，在硬骨鱼中具有广泛的宿主范围。虽然已经报道了许多巨细胞病毒分离株的全基因组序列，但该病毒的大多数基因的功能尚不清楚。在这项研究中，我们选择了两个巨细胞病毒免疫原，P247和P523，这是在宿主感染过程中表达，并在DNA疫苗的形式（pCN 247和pCN 523分别），引起了对致死性巨细胞病毒攻击大菱鲆（Scophthalmus maximus）模型的强保护性。与对照鱼相比，用pCN 247和pCN 523接种的鱼表现出组织中病毒载量的显著降低和高水平的存活率。免疫应答分析显示，pCN 247和pCN 523（i）诱导特异性血清抗体的产生，（ii）引起细胞毒性免疫细胞和对二次抗原刺激应答的特异性记忆免疫细胞的产生，以及（iii）上调参与先天性和适应性免疫的基因的表达。为了研究P247和P523在病毒感染中的潜在作用，用siRNA敲低P247和P523的表达。随后的体内感染研究表明，P247和P523敲低显著损害病毒复制。此外，全基因组转录组分析显示，P247和P523敲低分别改变了26和41个病毒基因的表达谱，参与病毒感染的各个方面。综上所述，这些结果表明，P247和P523诱导保护性免疫的硬骨鱼和病毒复制所必需的基本作用。这些观察结果提供了第一个证据，表明病毒免疫原的保护性与其在病毒复制中的生物学意义之间可能存在联系。
Megalocytivirus is a DNA virus with a broad host range among teleost fish. Although the complete genome sequences of a number of megalocytivirus isolates have been reported, the functions of most of the genes of this virus are unknown. In this study, we selected two megalocytivirus immunogens, P247 and P523, which were expressed during host infection and, when in the form of DNA vaccines (pCN247 and pCN523 respectively), elicited strong protectivity against lethal megalocytivirus challenge in a turbot (Scophthalmus maximus) model. Compared to control fish, fish vaccinated with pCN247 and pCN523 exhibited drastically reduced viral loads in tissues and high levels of survival rates. Immune response analysis showed that pCN247 and pCN523 (i) induced production of specific serum antibodies, (ii) caused generation of cytotoxic immune cells and specific memory immune cells that responded to secondary antigen stimulation, and (iii) upregulated the expression of genes involved in innate and adaptive immunity. To examine the potential role of P247 and P523 in viral infection, the expression of P247 and P523 was knocked down by siRNA. Subsequent in vivo infection study showed that P247 and P523 knockdown significantly impaired viral replication. Furthermore, whole-genome transcriptome analysis revealed that P247 and P523 knockdown altered the expression profiles of 26 and 41 viral genes, respectively, putatively participating in diverse aspects of viral infection. Taken together, these results indicate that P247 and P523 induce protective immunity in teleost and play fundamental roles essential to viral replication. These observations provide the first evidence that suggests a likely link between the protectivity of viral immunogens and their biological significance in viral replication.
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