Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Kunming, Yunnan 650223, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
Cytokine. 2021 Feb;138:155388. doi: 10.1016/j.cyto.2020.155388. Epub 2020 Nov 30.
Chinese tree shrews (Tupaia belangeri chinensis) are increasingly used as an alternative experimental animal to non-human primates in studying viral infections. Guanylate-binding proteins (GBP) belong to interferon (IFN)-inducible GTPases and defend the mammalian cell interior against diverse invasive pathogens. Previously, we identified five tree shrew GBP genes (tGBP1, tGBP2, tGBP4, tGBP5, and tGBP7) and found that tGBP1 showed antiviral activity against vesicular stomatitis virus (VSV) and type 1 herpes simplex virus (HSV-1) infections. Here, we showed that the anti-VSV activity of tGBP1 was independent of its GTPase activity and isoprenylation. In response to VSV infection, instead of regulating IFN expression and autophagy, tGBP1 competed with the VSV nucleocapsid (N) protein in binding to the VSV phosphoprotein (VSV-P), leading to the repression of the primary transcription of the VSV genome. These observations constitute the first report of the potential mechanism underlying the inhibition of VSV by GBP1.
树鼩（Tupaia belangeri chinensis）越来越多地被用作替代非人类灵长类动物的实验动物，用于研究病毒感染。鸟苷酸结合蛋白（GBP）属于干扰素（IFN）诱导的 GTPase，可抵御哺乳动物细胞内部的多种入侵病原体。先前，我们鉴定了五个树鼩 GBP 基因（tGBP1、tGBP2、tGBP4、tGBP5 和 tGBP7），并发现 tGBP1 对水疱性口炎病毒（VSV）和 1 型单纯疱疹病毒（HSV-1）感染具有抗病毒活性。在这里，我们表明 tGBP1 的抗 VSV 活性与其 GTPase 活性和异戊烯化无关。在响应 VSV 感染时，tGBP1 不是通过调节 IFN 表达和自噬来发挥作用，而是与 VSV 核衣壳（N）蛋白竞争与 VSV 磷蛋白（VSV-P）结合，从而抑制 VSV 基因组的初级转录。这些观察结果构成了 GBP1 抑制 VSV 的潜在机制的首次报道。
