Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. Feb 12, 2018; 7(1): 10-20
Published online Feb 12, 2018. doi: 10.5501/wjv.v7.i1.10
Identification of various cell culture models for the study of Zika virus
Kiyoshi Himmelsbach, Eberhard Hildt
Kiyoshi Himmelsbach, Eberhard Hildt, Department of Virology, Paul-Ehrlich-Institut, Langen 63225, Germany
Eberhard Hildt, Center for Infection Research (DZIF), Braunschweig 38124, Germany
Author contributions: Himmelsbach K designed and performed the experiments, analyzed the data and wrote the manuscript; Hildt E coordinated the research, analyzed the data and edited the manuscript.
Supported by the Federal Ministry of Health (BMG) to Hildt E.
Conflict-of-interest statement: There are no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Eberhard Hildt, PhD, Professor, Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, Langen 63225, Germany.
Telephone: +49-610-3775411 Fax: +49-610-3771273
Received: October 25, 2017
Peer-review started: October 27, 2017
First decision: November 23, 2017
Revised: December 6, 2017
Accepted: December 13, 2017
Article in press: December 13, 2017
Published online: February 12, 2018

To identify cell culture models supportive for Zika virus (ZIKV) replication.


Various human and non-human cell lines were infected with a defined amount of ZIKV Polynesia strain. Cells were analyzed 48 h post infection for the amount of intracellular and extracellular viral genomes and infectious viral particles by quantitative real-time PCR and virus titration assay. The extent of replication was monitored by immunofluorescence and western blot analysis by using Env and NS1 specific antibodies. Innate immunity was assayed by luciferase reporter assay and immunofluorescence analysis.


All investigated cell lines except CHO cells supported infection, replication and release of ZIKV. While in infected A549 and Vero cells a pronounced cytopathic effect was observed COS7, 293T and Huh7.5 cells were most resistant. Although the analyzed cell lines released comparable amounts of viral genomes to the supernatant significant differences were found for the number of infectious viral particles. The neuronal cell lines N29.1 and SH-SY5Y released 100 times less infectious viral particles than Vero-, A549- or 293T-cells. However there is no strict correlation between the amount of produced viral particles and the induction of an interferon response in the analyzed cell lines.


The investigated cell lines with their different tissue origins and diverging ZIKV susceptibility display a toolbox for ZIKV research.

Keywords: Zika virus, Cell lines, Quantitative real-time PCR, Plaque assay, Interferon

Core tip: In this study ten different cell lines, human and non-human, from various tissues (e.g., hepatocytes, keratinocytes and neuronal cells) were tested upon their susceptibility to Zika virus (ZIKV) infection. Except CHO cells all cells supported ZIKV life cycle, but differed in parts strongly in the intracellular and released amount of infectious viral particles. Investigating the interferon response showed no clear correlation between high and low producer cell lines.