鸟苷酸结合蛋白 (GBP) 5 是一种干扰素诱导细胞因子，具有广泛的抗病毒活性。最近，GBP5 已被证明可以拮抗许多包膜病毒的糖蛋白，部分是通过破坏宿主酶弗林蛋白酶来实现的。在这里，我们发现 GBP5 强烈损害病毒颗粒的感染性，这些病毒颗粒不仅携带依赖于弗林蛋白酶裂解而具有感染性的病毒糖蛋白，还包括 HIV-1 和鼠白血病病毒的包膜 (Env) 糖蛋白以及严重急性呼吸道病毒的刺突 (S) 糖蛋白。综合征冠状病毒 2 (SARS-CoV-2) - 以及不依赖于弗林蛋白酶裂解的病毒糖蛋白：水泡性口炎病毒糖蛋白和 SARS-CoV S。我们观察到 GBP5 破坏了正确的 N 连接蛋白糖基化并减少了病毒糖蛋白的掺入糖蛋白转化为病毒颗粒。 GBP5 表达也会改变细胞蛋白 CD4 的糖基化。流式细胞术分析表明，GBP5 表达降低了细胞表面 HIV-1 Env 以及 SARS-CoV 和 SARS-CoV-2 的 S 糖蛋白的水平。我们的数据表明，在所使用的实验条件下，抑制弗林蛋白酶介导的糖蛋白裂解并不是 GBP5 的主要抗病毒作用机制。相反，这种拮抗作用似乎与糖蛋白向质膜的运输受损有关。这些结果为细胞宿主先天免疫反应对病毒糖蛋白功能的广泛拮抗作用提供了新的见解。有包膜病毒的表面含有病毒包膜糖蛋白，它是促进病毒附着和进入的重要结构成分，同时也充当宿主适应性免疫的靶标系统。在这项研究中，我们表明 GBP5 在病毒产生细胞中的表达改变了多个病毒家族中病毒糖蛋白的糖基化、细胞表面表达和病毒体掺入。这项研究为宿主细胞抗病毒因子 GBP5 对蛋白质糖基化和运输的广泛影响提供了新的见解。

Guanylate-binding protein (GBP) 5 is an interferon-inducible cellular factor with broad anti-viral activity. Recently, GBP5 has been shown to antagonize the glycoproteins of a number of enveloped viruses, in part by disrupting the host enzyme furin. Here we show that GBP5 strongly impairs the infectivity of virus particles bearing not only viral glycoproteins that depend on furin cleavage for infectivity-the envelope (Env) glycoproteins of HIV-1 and murine leukemia virus and the spike (S) glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-but also viral glycoproteins that do not depend on furin cleavage: vesicular stomatitis virus glycoprotein and SARS-CoV S. We observe that GBP5 disrupts proper N-linked protein glycosylation and reduces the incorporation of viral glycoproteins into virus particles. The glycosylation of the cellular protein CD4 is also altered by GBP5 expression. Flow cytometry analysis shows that GBP5 expression reduces the cell-surface levels of HIV-1 Env and the S glycoproteins of SARS-CoV and SARS-CoV-2. Our data demonstrate that, under the experimental conditions used, inhibition of furin-mediated glycoprotein cleavage is not the primary anti-viral mechanism of action of GBP5. Rather, the antagonism appears to be related to impaired trafficking of glycoproteins to the plasma membrane. These results provide novel insights into the broad antagonism of viral glycoprotein function by the cellular host innate immune response.The surface of enveloped viruses contains viral envelope glycoproteins, an important structural component facilitating virus attachment and entry while also acting as targets for the host adaptive immune system. In this study, we show that expression of GBP5 in virus-producer cells alters the glycosylation, cell-surface expression, and virion incorporation of viral glycoproteins across several virus families. This research provides novel insights into the broad impact of the host cell anti-viral factor GBP5 on protein glycosylation and trafficking.