Next Article in Journal
THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1
Next Article in Special Issue
Integrated MicroRNA and mRNA Profiling in Zika Virus-Infected Neurons
Previous Article in Journal
Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus
Previous Article in Special Issue
Differential Zika Virus Infection of Testicular Cell Lines
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Viruses 2019, 11(2), 157; https://doi.org/10.3390/v11020157

The Roles of prM-E Proteins in Historical and Epidemic Zika Virus-mediated Infection and Neurocytotoxicity

1
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2
Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Université de La Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, Sainte-Clotilde, 97400 La Réunion, France
3
Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA
4
Department of Microbiology-Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
5
Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
6
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 18 December 2018 / Revised: 3 February 2019 / Accepted: 9 February 2019 / Published: 14 February 2019
(This article belongs to the Special Issue New Advances on Zika Virus Research)
Full-Text   |   PDF [3474 KB, uploaded 14 February 2019]   |  
  |   Review Reports

Abstract

The Zika virus (ZIKV) was first isolated in Africa in 1947. It was shown to be a mild virus that had limited threat to humans. However, the resurgence of the ZIKV in the most recent Brazil outbreak surprised us because it causes severe human congenital and neurologic disorders including microcephaly in newborns and Guillain-Barré syndrome in adults. Studies showed that the epidemic ZIKV strains are phenotypically different from the historic strains, suggesting that the epidemic ZIKV has acquired mutations associated with the altered viral pathogenicity. However, what genetic changes are responsible for the changed viral pathogenicity remains largely unknown. One of our early studies suggested that the ZIKV structural proteins contribute in part to the observed virologic differences. The objectives of this study were to compare the historic African MR766 ZIKV strain with two epidemic Brazilian strains (BR15 and ICD) for their abilities to initiate viral infection and to confer neurocytopathic effects in the human brain’s SNB-19 glial cells, and further to determine which part of the ZIKV structural proteins are responsible for the observed differences. Our results show that the historic African (MR766) and epidemic Brazilian (BR15 and ICD) ZIKV strains are different in viral attachment to host neuronal cells, viral permissiveness and replication, as well as in the induction of cytopathic effects. The analysis of chimeric viruses, generated between the MR766 and BR15 molecular clones, suggests that the ZIKV E protein correlates with the viral attachment, and the C-prM region contributes to the permissiveness and ZIKV-induced cytopathic effects. The expression of adenoviruses, expressing prM and its processed protein products, shows that the prM protein and its cleaved Pr product, but not the mature M protein, induces apoptotic cell death in the SNB-19 cells. We found that the Pr region, which resides on the N-terminal side of prM protein, is responsible for prM-induced apoptotic cell death. Mutational analysis further identified four amino-acid residues that have an impact on the ability of prM to induce apoptosis. Together, the results of this study show that the difference of ZIKV-mediated viral pathogenicity, between the historic and epidemic strains, contributed in part the functions of the structural prM-E proteins. View Full-Text
Keywords: Zika virus; prM-E proteins; viral pathogenicity; virus attachment; viral replication; viral permissiveness; viral survival; apoptosis; cytopathic effects; mutagenesis; chimeric viruses; human brain glial cells Zika virus; prM-E proteins; viral pathogenicity; virus attachment; viral replication; viral permissiveness; viral survival; apoptosis; cytopathic effects; mutagenesis; chimeric viruses; human brain glial cells
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Li, G.; Bos, S.; Tsetsarkin, K.A.; Pletnev, A.G.; Desprès, P.; Gadea, G.; Zhao, R.Y. The Roles of prM-E Proteins in Historical and Epidemic Zika Virus-mediated Infection and Neurocytotoxicity. Viruses 2019, 11, 157.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top