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N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle
Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification. Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated. The prM protein of all ZIKV strains contains a single N-linked glycosylation site,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552079/ https://www.ncbi.nlm.nih.gov/pubmed/32842538 http://dx.doi.org/10.3390/v12090925 |
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author | Gwon, Yong-Dae Zusinaite, Eva Merits, Andres Överby, Anna K. Evander, Magnus |
author_facet | Gwon, Yong-Dae Zusinaite, Eva Merits, Andres Överby, Anna K. Evander, Magnus |
author_sort | Gwon, Yong-Dae |
collection | PubMed |
description | Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification. Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated. The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein. Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking. Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant. Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions. The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment. The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization. In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker. To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly. |
format | Online Article Text |
id | pubmed-7552079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75520792020-10-14 N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle Gwon, Yong-Dae Zusinaite, Eva Merits, Andres Överby, Anna K. Evander, Magnus Viruses Article Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification. Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated. The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein. Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking. Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant. Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions. The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment. The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization. In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker. To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly. MDPI 2020-08-23 /pmc/articles/PMC7552079/ /pubmed/32842538 http://dx.doi.org/10.3390/v12090925 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gwon, Yong-Dae Zusinaite, Eva Merits, Andres Överby, Anna K. Evander, Magnus N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle |
title | N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle |
title_full | N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle |
title_fullStr | N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle |
title_full_unstemmed | N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle |
title_short | N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle |
title_sort | n-glycosylation in the pre-membrane protein is essential for the zika virus life cycle |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552079/ https://www.ncbi.nlm.nih.gov/pubmed/32842538 http://dx.doi.org/10.3390/v12090925 |
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