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Home / Equine Research Bank / Viruses / The N-glycosylation of Equine Tetherin Affects Antiviral Act...
Viruses2020; 12(2); 220; doi: 10.3390/v12020220

The N-glycosylation of Equine Tetherin Affects Antiviral Activity by Regulating Its Subcellular Localization.

Abstract: 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.
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Publication Date: 2020-02-16 PubMed ID: 32079099PubMed Central: PMC7077275DOI: 10.3390/v12020220Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article investigates how the glycosylation of the protein tetherin impacts its antiviral properties, specifically in horses. The study has found that mutations affecting N-glycosylation sites can weaken the antiviral activity of the protein, mainly by affecting its transport within cells and altering its location.

Overview of Tetherin

  • Tetherin, also known as the bone marrow stromal antigen 2, is a type of protein. It was first recognized for its ability to inhibit the release of various viruses, such as retroviruses, through a mechanism known as “physical tethering”.
  • Technically, this is a transmembrane protein, which means it straddles the boundary of the cell, partially inside and partially outside. This positioning allows it to interact with the viruses that try to push out of the cells.

Role of N-Glycosylation

  • Glycosylation is a process where carbohydrate molecules get added to proteins; in the case of N-glycosylation, these carbohydrates are added at specific nitrogen points within the protein structure.
  • The function that glycosylation plays in tetherin’s antiviral activity has been a topic of debate and was the focus of this study.
  • Researchers found that when they induced mutations at the N-glycosylation sites of the equine tetherin (eqTHN), the protein’s antiviral activity was diminished. This altered form of the protein also showed reduced expression at the plasma membrane, the outer boundary of the cell.

Impacts on Cellular Localization and Transport

  • The variants of eqTHN with mutated N-glycosylation sites showed a significant colocalization with the endoplasmic reticulum, endosomes, and certain proteins (ER, CD63, LAMP1), unlike the original version of the protein.
  • This suggests that N-glycosylation plays a role in determining the subcellular location of tetherin, subsequently impacting its functional efficiency.
  • The research further found that the N-glycosylation impacts the transportation of eqTHN within cells, not by affecting the process of endocytosis (uptake of material into a cell), but by influencing the anterograde trafficking (movement of molecules from the cell’s center towards its periphery) of the protein.

Conclusion and Implications

  • The findings suggest that the N-glycosylation of tetherin is critical for the protein’s antiviral activity, as it regulates its localization within the cell.
  • Uncovering this link could pave the way for better understanding the functioning of this crucial restriction factor, potentially informing the development of new antiviral therapies.

Cite This Article

APA
Bai B, Wang XF, Zhang M, Na L, Zhang X, Zhang H, Yang Z, Wang X. (2020). The N-glycosylation of Equine Tetherin Affects Antiviral Activity by Regulating Its Subcellular Localization. Viruses, 12(2), 220. https://doi.org/10.3390/v12020220

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 12
Issue: 2
PII: 220

Researcher Affiliations

Bai, Bowen
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Wang, Xue-Feng
  • 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.
Zhang, Mengmeng
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Na, Lei
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Zhang, Xiangmin
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Zhang, Haili
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Yang, Zhibiao
  • Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Wang, Xiaojun
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.

MeSH Terms

  • Animals
  • Bone Marrow Stromal Antigen 2 / genetics
  • Bone Marrow Stromal Antigen 2 / metabolism
  • Endocytosis
  • Glycosylation
  • HEK293 Cells
  • Horses
  • Humans
  • Intracellular Space / metabolism
  • Mutation
  • Protein Transport
  • Virus Release

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 4 times.
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