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N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology. (Magnus Evander)ORCID iD: 0000-0002-0703-4188
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology. (Anna Överby)ORCID iD: 0000-0001-6553-0940
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2020 (English)In: Viruses, E-ISSN 1999-4915, Vol. 12, no 9, article id 925Article in journal (Refereed) Published
Abstract [en]

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 areN-glycosylated. The prM protein of all ZIKV strains contains a singleN-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 theN-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 thatN-glycosylation was necessary for effective secretion of ZIKV virions. The absence of theN-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 theN-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker. To conclude, we show that the prMN-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.

Place, publisher, year, edition, pages
MDPI, 2020. Vol. 12, no 9, article id 925
Keywords [en]
Zika virus, N-glycosylation, pre-membrane, envelope, virus life cycle
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-176452DOI: 10.3390/v12090925ISI: 000580340900001PubMedID: 32842538Scopus ID: 2-s2.0-85089933821OAI: oai:DiVA.org:umu-176452DiVA, id: diva2:1502515
Available from: 2020-11-20 Created: 2020-11-20 Last updated: 2024-01-17Bibliographically approved

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Yong-Dae, KwonÖverby, Anna K.Evander, Magnus

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Umeå Centre for Microbial Research (UCMR)Department of Clinical MicrobiologyMolecular Infection Medicine Sweden (MIMS)
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