近日，国际著名病毒学杂志《Journal of Virology》上在线发表中国农业科学院哈尔滨兽医研究所猪烈性传染病创新团队仇华吉研究员的一篇研究论文，团队经过系统研究发现了一个具有抗猪瘟病毒活性的干扰素刺激基因(ISG)即鸟苷酸结合蛋白1(GBP1)，并阐明了其抗病毒机制。此项研究发现，不仅有助于深入了解宿主抗病毒机理，同时也为揭示猪瘟病毒逃避宿主抗病毒策略提供了线索。此外，抗病毒ISG研究对创新猪瘟防控策略具有重要意义，并为猪瘟病毒所在的黄病毒科其它成员的抗病毒研究提供了参考。
Guanylate-binding protein 1, an interferon-induced GTPase, exerts an antiviral activity against classical swine fever virus depending on its GTPase activity
原文摘要：
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.