State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Viruses. 2020 Feb 16;12(2):220. doi: 10.3390/v12020220.
Tetherin is an interferon-inducible type II transmembrane glycoprotein which inhibits the release of viruses, including retroviruses, through a "physical tethering" model. However, the role that the glycosylation of tetherin plays in its antiviral activity remains controversial. In this study, we found that mutation of N-glycosylation sites resulted in an attenuation of the antiviral activity of equine tetherin (eqTHN), as well as a reduction in the expression of eqTHN at the plasma membrane (PM). In addition, eqTHN N-glycosylation mutants colocalize obviously with ER, CD63, LAMP1 and endosomes, while WT eqTHN do not. Furthermore, we also found that N-glycosylation impacts the transport of eqTHN in the cell not by affecting the endocytosis, but rather by influencing the anterograde trafficking of the protein. These results suggest that the N-glycosylation of eqTHN is important for the antiviral activity of the protein through regulating its normal subcellular localization. This finding will enhance our understanding of the function of this important restriction factor.
tetherin 是一种干扰素诱导的 II 型跨膜糖蛋白，通过“物理 tethering”模型抑制病毒（包括逆转录病毒）的释放。然而， tetherin 的糖基化在其抗病毒活性中的作用仍存在争议。在本研究中，我们发现 N-糖基化位点的突变导致马 tetherin（eqTHN）的抗病毒活性减弱，以及质膜（PM）上 eqTHN 的表达减少。此外，eqTHN N-糖基化突变体与 ER、CD63、LAMP1 和内体明显共定位，而 WT eqTHN 则没有。此外，我们还发现，N-糖基化不是通过影响内吞作用，而是通过影响蛋白的正向运输来影响 eqTHN 的细胞内运输。这些结果表明，eqTHN 的 N-糖基化通过调节其正常的亚细胞定位对蛋白的抗病毒活性很重要。这一发现将增强我们对这一重要限制因子功能的理解。
