Porcine ISG15 modulates the antiviral response during pseudorabies virus replication
Porcine ISG15 modulates the antiviral response during pseudorabies virus replication
复制标题
猪 ISG15 调节伪狂犬病病毒复制过程中的抗病毒反应
DOI：
10.1016/j.gene.2018.09.007
复制
发表时间：
2018-12-30
期刊：
影响因子：
3.5
通讯作者：
Chang, Hongtao
中科院分区：
文献类型：
--
作者：
Liu, Huimin;Li, Shuangshuang;Chang, Hongtao
伪狂犬病病毒（Pseudorabies virus，PRV）是猪的重要病原之一，给养猪业造成了巨大的经济损失。Ⅰ型干扰素（IFN）是天然免疫系统中的一种，在病毒感染的初期起着至关重要的作用。ISG 15是一种IFN刺激的泛素样蛋白，在病毒感染期间高度增加，并参与IFN介导的抗病毒免疫应答。然而，猪ISG 15（pISG 15）在PRV感染中的功能作用受到的关注有限。在这项研究中，我们建立了一个PK 15诱导细胞系稳定表达pISG 15基因，并研究了潜在的抗PRV反应的pISG 15。我们证明了pISG 15在PRV感染的早期被上调，并且pISG 15过表达通过降低PRV的病毒滴度和mRNA水平有效地抑制PRV复制，并且还增加IFN-β的表达和ISRE启动子的激活。然而，通过siRNA敲低pISG 15并不影响PRV的复制，并且增强了IFN-I介导的信号传导，导致PRV感染过程中的抗病毒应答增加。结果表明，pISG 15在细胞抗PRV的免疫应答中具有潜在的免疫调节作用。
Pseudorabies virus (PRV) is one of the most vital pathogens of swine, leading to huge economic losses to the pig industry. Functioning in innate immunity, type-I interferon (IFN) plays a vital role in initial stage of viral infection. ISG15, an IFN-stimulated ubiquitin-like protein, is highly increased during virus infection and participates in the IFN-mediated antiviral immune response. However, limited attention has been paid to the functional role of porcine ISG15 (pISG15) in PRV infection. In this study, we generated a PK15 inducible cell line stably expressing the pISG15 gene and investigated the potential anti-PRV response of pISG15. We demonstrated that pISG15 was upregulated in an early stage of PRV infection, and pISG15 overexpression efficiently inhibited PRV replication by reducing the viral titers and mRNA levels of PRV, and also increased expression of IFN-beta and activation of the ISRE promoter. However, knockdown of pISG15 by siRNA did not affect PRV replication, and potentiated IFN-I-mediated signaling, resulting in an increase in antiviral response in the process of PRV infection. The results showed that pISG15 has a potential immunodulatory role in cellular antiviral response against PRV.