PDF(Pubmed)
Abstract：
Infectious bursal disease (IBD) is an acute and fatal immunosuppressive disease caused by infectious bursal disease virus (IBDV). As an obligate intracellular parasite, IBDV infection is strictly regulated by host factors. Knowledge on the antiviral activity and possible mechanism of host factors might provide the theoretical basis for the prevention and control of IBD. In this study, RNA-sequencing results indicated that many host factors were induced by IBDV infection, among which the expression levels of OASL (2´,5´-oligadenylate synthetase-like protein) was significantly upregulated. OASL overexpression significantly inhibited IBDV replication, whereas OASL knockdown promoted IBDV replication. Interestingly, the antiviral ability of OASL was independent of its canonical enzymatic activity, i.e., OASL targeted viral protein VP2 for degradation, depending on the autophagy receptor p62/SQSTM1 in the autophagy pathway. Additionally, the 316 lysine (K) of VP2 was the key site for autophagy degradation, and its replacement with arginine disrupted VP2 degradation induced by OASL and enhanced IBDV replication. Importantly, our results for the first time indicate a unique and potent defense mechanism of OASL against double-stranded RNA virus by interaction with viral proteins, which leads to their degradation.
OBJECTIVE: OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.
OBJECTIVE: OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.
摘要：
传染性法氏囊病(IBD)是由传染性法氏囊病病毒(IBDV)引起的一种急性致死性免疫抑制性疾病。作为一种专性细胞内寄生虫，IBDV感染受到宿主因子的严格调控。了解宿主因子的抗病毒活性及可能的作用机制,可为IBD的防治提供理论依据。在这项研究中,RNA测序结果表明,IBDV感染可诱导多种宿主因子,其中OASL的表达水平(2'，5'-寡腺苷酸合成酶样蛋白）显着上调。OASL过表达显著抑制IBDV复制,而OASL敲除促进IBDV复制。有趣的是,OASL的抗病毒能力与其经典酶活性无关，即，OASL靶向病毒蛋白VP2的降解，取决于自噬途径中的自噬受体p62/SQSTM1。此外,VP2的316赖氨酸（K）是自噬降解的关键位点，用精氨酸代替它破坏了OASL诱导的VP2降解并增强了IBDV的复制。重要的是,我们的研究结果首次表明了OASL通过与病毒蛋白相互作用对双链RNA病毒的独特而有效的防御机制，这导致了他们的退化。
目标：OASL(2'，5'-寡腺苷酸合成酶样蛋白）对哺乳动物中的单链RNA病毒具有广谱抗病毒作用，潜在的作为一个有希望的新的抗病毒策略的目标。然而,它在抑制双链RNA病毒（dsRNA病毒）复制中的作用，如传染性法氏囊病病毒（IBDV），鸟类物种尚不清楚。我们的发现表明了OASL针对dsRNA病毒的独特而有效的防御机制。先前已经在哺乳动物中显示,OASL通过增加干扰素产生来抑制病毒复制。我们研究的开创性方面是发现OASL具有与IBDV病毒蛋白VP2相互作用并靶向降解的能力，从而发挥其抗病毒作用。我们的结果揭示了禽类天然抗病毒免疫应答与IBDV感染之间的相互作用。我们的研究不仅增强了我们对鸟类防御病毒感染的理解，而且还可以为家禽疾病管理策略提供信息。
目标：OASL(2'，5'-寡腺苷酸合成酶样蛋白）对哺乳动物中的单链RNA病毒具有广谱抗病毒作用，潜在的作为一个有希望的新的抗病毒策略的目标。然而,它在抑制双链RNA病毒（dsRNA病毒）复制中的作用，如传染性法氏囊病病毒（IBDV），鸟类物种尚不清楚。我们的发现表明了OASL针对dsRNA病毒的独特而有效的防御机制。先前已经在哺乳动物中显示,OASL通过增加干扰素产生来抑制病毒复制。我们研究的开创性方面是发现OASL具有与IBDV病毒蛋白VP2相互作用并靶向降解的能力，从而发挥其抗病毒作用。我们的结果揭示了禽类天然抗病毒免疫应答与IBDV感染之间的相互作用。我们的研究不仅增强了我们对鸟类防御病毒感染的理解，而且还可以为家禽疾病管理策略提供信息。
