Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Dengue Virus Antibodies Enhance Zika Virus Infection

Lauren M. Paul, Eric R. Carlin, Meagan M. Jenkins, Amanda L. Tan, Carolyn M. Barcellona, Cindo O. Nicholson, Lydie Trautmann, Scott F. Michael, Sharon Isern
doi: https://doi.org/10.1101/050112
Lauren M. Paul
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric R. Carlin
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Meagan M. Jenkins
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amanda L. Tan
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carolyn M. Barcellona
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cindo O. Nicholson
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lydie Trautmann
2U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America
3Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott F. Michael
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sharon Isern
1Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, Florida, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: sisern@fgcu.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Background For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases endemic in the same regions. Recent reports of severe disease associated with ZIKV, including Guillain-Barré syndrome and severe fetal abnormalities, have greatly heightened awareness. Given its recent history of rapid spread in immune naïve populations, it is anticipated that ZIKV will continue to spread in the Americas and globally in regions where competent Aedes mosquito vectors are found. Globally, dengue virus (DENV) is the most common mosquito-transmitted human flavivirus and is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through a mechanism known as antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. However, response to DENV antibodies has not yet been investigated.

Methodology / Principal Findings We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection.

Conclusions / Significance Our results suggest that pre-existing DENV immunity will enhance ZIKV infection in vivo and may increase disease severity. A clear understanding of the interplay between ZIKV and DENV will be critical in informing public health responses in regions where these viruses co-circulate and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

Author Summary Recent reports of severe disease, including developmental problems in newborns, have greatly heightened public health awareness of Zika virus (ZIKV), a mosquito-transmitted virus for which there is no vaccine or treatment. It is anticipated that ZIKV will continue to spread in the Americas and globally in regions where competent mosquitoes are found. Dengue virus (DENV), a closely related mosquito-transmitted virus is well-established in regions of recent ZIKV introduction and spread. It is increasingly common that individuals living in these regions may have had a prior DENV infection or may be infected with DENV and ZIKV at the same time. However, very little is known about the impact of DENV infections on ZIKV disease severity. In this study, we tested the ability of antibodies against DENV to prevent or enhance ZIKV infection in cell culture-based assays. We found that DENV antibodies can greatly enhance ZIKV infection in cells.

Our results suggest that ZIKV infection in individuals that had a prior DENV infection may experience more severe clinical manifestations. The results of this study provide a better understanding of the interplay between ZIKV and DENV infections that can serve to inform public health responses and vaccine strategies.

Footnotes

  • ↵¶ SI and SFM are Joint Senior Authors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted April 25, 2016.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Dengue Virus Antibodies Enhance Zika Virus Infection
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Dengue Virus Antibodies Enhance Zika Virus Infection
Lauren M. Paul, Eric R. Carlin, Meagan M. Jenkins, Amanda L. Tan, Carolyn M. Barcellona, Cindo O. Nicholson, Lydie Trautmann, Scott F. Michael, Sharon Isern
bioRxiv 050112; doi: https://doi.org/10.1101/050112
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Dengue Virus Antibodies Enhance Zika Virus Infection
Lauren M. Paul, Eric R. Carlin, Meagan M. Jenkins, Amanda L. Tan, Carolyn M. Barcellona, Cindo O. Nicholson, Lydie Trautmann, Scott F. Michael, Sharon Isern
bioRxiv 050112; doi: https://doi.org/10.1101/050112

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4235)
  • Biochemistry (9136)
  • Bioengineering (6784)
  • Bioinformatics (24001)
  • Biophysics (12129)
  • Cancer Biology (9534)
  • Cell Biology (13778)
  • Clinical Trials (138)
  • Developmental Biology (7636)
  • Ecology (11702)
  • Epidemiology (2066)
  • Evolutionary Biology (15513)
  • Genetics (10644)
  • Genomics (14326)
  • Immunology (9483)
  • Microbiology (22839)
  • Molecular Biology (9090)
  • Neuroscience (48995)
  • Paleontology (355)
  • Pathology (1482)
  • Pharmacology and Toxicology (2570)
  • Physiology (3846)
  • Plant Biology (8331)
  • Scientific Communication and Education (1471)
  • Synthetic Biology (2296)
  • Systems Biology (6192)
  • Zoology (1301)