Evidence map›Paper›PMID 28931684›Full record

ArticleJournal of virology2017

Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated and Defective in Neuroinvasion.

Arun S Annamalai, Aryamav Pattnaik, Bikash R Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep L X Vu, Gustavo Delhon, Fernando A Osorio, Thomas M Petro and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
14.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 106 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Zika Virus: A Tale of Two Lineages.Pathogens (Basel, Switzerland) · 2025
    Review
  6. Review
  7. Article
  8. Evolution of Zika virus inVirus evolution · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. A review on Zika vaccine development.Pathogens and disease · 2024
    Review
  13. Article
  14. Reverse Genetics of Zika Virus Using a Bacterial Artificial Chromosome.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Arun S AnnamalaiSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Aryamav PattnaikSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Bikash R SahooSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Ezhumalai MuthukrishnanDepartment of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Sathish Kumar NatarajanDepartment of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
David SteffenSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Hiep L X VuDepartment of Animal Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Gustavo DelhonSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Fernando A OsorioSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Thomas M PetroNebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Shi-Hua XiangSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Asit K PattnaikSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA apattnaik2@unl.edu.
University of Nebraska–Lincoln · US

Funding

Nebraska Center for VirologyP30GM103509 · NIGMS · UNIVERSITY OF NEBRASKA LINCOLN · PI WOOD, CHARLES · 2012 to 2014
$3.3M
NIGMS NIH HHS P30 GM103509
6 · The paper itself

Abstract

Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the recent outbreaks. In the present study, we investigated the roles of this sequence motif and glycosylation of the E protein in the pathogenicity of ZIKV. We first constructed a stable full-length cDNA clone of ZIKV in a novel linear vector from which infectious virus was recovered. The recombinant ZIKV generated from the infectious clone, which contains the VNDT motif, is highly pathogenic and causes lethality in a mouse model. In contrast, recombinant viruses from which the VNDT motif is deleted or in which the N-linked glycosylation site is mutated by single-amino-acid substitution are highly attenuated and nonlethal. The mutant viruses replicate poorly in the brains of infected mice when inoculated subcutaneously but replicate well following intracranial inoculation. Our findings provide the first evidence that N-linked glycosylation of the E protein is an important determinant of ZIKV virulence and neuroinvasion.

Indexed as

Amino Acid MotifsAnimalsBrainCell LineChlorocebus aethiopsDisease Models, AnimalEvolution, MolecularGlycosylationHumansMiceMosquito VectorsMutationPhylogenyVero CellsViral Envelope ProteinsVirulence FactorsViral Envelope ProteinsVirulence FactorsattenuationE protein glycosylationneuroinvasionZika virus

Identifiers

PMID28931684
PMCPMC5686755
OpenAlexW2755187147

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.