Evidence map›Paper›PMID 27555311›Full record

ArticlemBio2016

A Full-Length Infectious cDNA Clone of Zika Virus from the 2015 Epidemic in Brazil as a Genetic Platform for Studies of Virus-Host Interactions and Vaccine Development.

Konstantin A Tsetsarkin, Heather Kenney, Rubing Chen, Guangping Liu, Hasmik Manukyan, Stephen S Whitehead, Majid Laassri, Konstantin Chumakov, Alexander G Pletnev

Open access · goldAbstract read
In one paragraph

Article in mBio, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 1 pooled it
22.4field-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

96 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.

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

36 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

9 authors at 3 institutions in 1 country.

Konstantin A TsetsarkinLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Heather KenneyLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Rubing ChenDepartment of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA.
Guangping LiuLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Hasmik ManukyanCenter for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Stephen S WhiteheadLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Majid LaassriCenter for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Konstantin ChumakovCenter for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0003-3002-6247
Alexander G PletnevLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA apletnev@niaid.nih.gov.
National Institutes of Health · USCenter for Biologics Evaluation and Research · USThe University of Texas Medical Branch at Galveston · US

Funding

Development Of New Approaches To Vaccines Against TBEV and West Nile VirusZIAAI000637 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI PLETNEV, ALEXANDER · 2009 to 2022
$19.1M
Laboratory And Preclinical Studies Of FlavivirusesZIAAI000891 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI WHITEHEAD, STEPHEN · 2009 to 2025
$17.5M
6 · The paper itself

Abstract

unlabelledAn arthropod-borne virus, Zika virus (ZIKV), has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barré syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the development of a reverse genetic system based on an epidemic ZIKV strain. Here, we describe the generation and characterization in cell cultures of an infectious cDNA clone of ZIKV isolated from the 2015 epidemic in Brazil. The cDNA-derived ZIKV replicated efficiently in a variety of cell lines, including those of both neuronal and placental origin. We observed that the growth of cDNA-derived virus was attenuated compared to the growth of the parental isolate in most cell lines, which correlates with substantial differences in sequence heterogeneity between these viruses that were determined by deep-sequencing analysis. Our findings support the role of genetic diversity in maintaining the replicative fitness of viral populations under changing conditions. Moreover, these results indicate that caution should be exercised when interpreting the results of reverse-genetics experiments in attempts to accurately predict the biology of natural viruses. Finally, a Vero cell-adapted cDNA clone of ZIKV was generated that can be used as a convenient platform for studies aimed at the development of ZIKV vaccines and therapeutics. IMPORTANCE: The availability of genetic tools and laboratory models determines the progress in understanding mechanisms of virus emergence and pathogenesis. Recent large-scale outbreaks of Zika virus (ZIKV) that were linked to complications during perinatal development and Guillain-Barré syndrome in adults emphasize the urgency for the development of a reverse-genetics system based on an epidemic ZIKV strain. Here, we report a stable infectious cDNA clone for ZIKV isolated during the 2015 epidemic in Brazil, as well as a Vero cell-adapted version of it, which will be used for virus-host interaction studies and vaccine development.

Indexed as

Cloning, MolecularBrazilCell LineDisease OutbreaksDNA, ComplementaryDNA, ViralHost-Pathogen InteractionsHumansReverse GeneticsViral VaccinesVirologyVirus CultivationZika VirusZika Virus InfectionDNA, ComplementaryDNA, ViralViral Vaccines

Identifiers

PMID27555311
PMCPMC4999549
OpenAlexW2509714578

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.