JV:我科学家发现新的抗猪瘟病毒分子

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记者2月25日从中国农业科学院哈尔滨兽医研究所获悉，该所研究人员发现了一个可抗猪瘟病毒活性的干扰素刺激基因“鸟苷酸结合蛋白1”，并阐明了其抗病毒机制。

猪瘟是一种高度接触性猪传染病，传播快、致死率高，每年给我国养猪业带来的损失可达数十亿元，被世界动物卫生组织列入须申报的动物疫病名录。我国在《国家中长期动物疫病防治规划》中将其列为优先防治的一类动物疫病。

据哈兽研所猪烈性传染病创新团队李连峰博士介绍，干扰素刺激基因，是使得宿主发挥抗病毒作用的一类效应分子，可靶向侵入、脱壳、病毒粒子释放等病毒复制周期环节。阻断其中某一环节，即可抑制病毒在机体内的存活。该团队的研究即以此入手。

在获得的多个干扰素刺激基因候选分子中，团队通过高通量筛选鉴定，最终证实“鸟苷酸结合蛋白1”为抗猪瘟病毒的干扰素刺激基因。

团队首席科学家仇华吉研究员解释说，该分子发挥抗病毒作用主要依赖其GTPase活性，而猪瘟病毒恰是利用自身NS5A蛋白与干扰素刺激基因相互作用，抑制后者的GTPase活性，进而干扰“鸟苷酸结合蛋白1”的抗病毒功能。

专家说，此发现有助于深入了解宿主抗病毒机理，也为揭示猪瘟病毒逃避宿主抗病毒策略提供了线索。结合抗病毒干扰素刺激基因开展研究，对创新猪瘟防控策略具有重要意义，并为猪瘟病毒所在黄病毒科其他成员的抗病毒研究提供了参考。

此研究结果已在国际著名病毒学杂志《Journal of Virology》上在线发表。

来源：新华网

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Guanylate-binding protein 1, an interferon-induced GTPase, exerts an antiviral activity against classical swine fever virus depending on its GTPase activity

Lian-Feng Li1, Jiahui Yu1, Yongfeng Li1, Jinghan Wang1, Su Li1, Lingkai Zhang1, Shui-Li Xia1, Qian Yang1, Xiao Wang1, Shaoxiong Yu1, Yuzi Luo1, Yuan Sun1, Yan Zhu2, Muhammad Munir3 and Hua-Ji Qiu1⇑

Many viruses trigger the type I interferon (IFN) pathway upon infection, resulting in the transcription of hundreds of interferon-stimulated genes (ISGs), which define the antiviral state of the host. Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious viral disease endangering the pig industry in many countries. However, anti-CSFV ISGs are poorly documented. Here, we screened 20 ISGs that are commonly induced by type I IFNs against CSFV in lentivirus-delivered cell lines, resulting in the identification of guanylate-binding protein 1 (GBP1) as a potent anti-CSFV ISG. We observed that overexpression of GBP1, an IFN-induced GTPase, remarkably suppressed CSFV replication, whereas knocking down the endogenous GBP1 expression by small interfering RNAs significantly promoted CSFV growth. Furthermore, we demonstrated that GBP1 acted mainly upon the early phase of CSFV replication and inhibited the translation efficiency of the internal ribosome entry site of CSFV. In addition, we found that GBP1 was upregulated at the transcriptional level in CSFV-infected PK-15 cells and in various organs of CSFV-infected pigs. Coimmunoprecipitation and GST pulldown assays revealed that GBP1 interacted with the NS5A protein of CSFV and this interaction was mapped in the N-terminal globular GTPase domain of GBP1. Interestingly, the K51 of GBP1, which is crucial for its GTPase activity, was essential for the inhibition of CSFV replication. We further showed that NS5A-GBP1 interaction inhibited GTPase activity, which was critical for its antiviral effect. Taken together, GBP1 is an anti-CSFV ISG whose action depends on its GTPase activity.

http://jvi.asm.org/content/early ... 7-abc1-6e2263fcbe7a