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N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle

Yong-Dae, Kwon, 1984- (author)
Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för klinisk mikrobiologi,Magnus Evander
Zusinaite, Eva (author)
Merits, Andres (author)
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Överby, Anna K., 1978- (author)
Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för klinisk mikrobiologi,Anna Överby
Evander, Magnus, 1959- (author)
Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för klinisk mikrobiologi,Magnus Evander
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 (creator_code:org_t)
2020-08-23
2020
English.
In: Viruses. - : MDPI. - 1999-4915. ; 12:9
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Keyword

Zika virus
N-glycosylation
pre-membrane
envelope
virus life cycle

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ref (subject category)
art (subject category)

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Zusinaite, Eva
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