The current epidemic of Zika virus (ZIKV) has underscored the urgency to establish experimental systems for studying viral replication and pathogenesis, and countermeasure development. Here we report two ZIKV replicon systems: a luciferase replicon that can differentiate between viral translation and RNA synthesis; and a stable luciferase replicon carrying cell line that can be used to screen and characterize inhibitors of viral replication. The transient replicon was used to evaluate the effect of an NS5 polymerase mutation on viral RNA synthesis and to analyze a known ZIKV inhibitor. The replicon cell line was developed into a 96-well format for antiviral testing. Compare with virus infection-based assay, the replicon cell line allows antiviral screening without using infectious virus. Collectively, the replicon systems have provided critical tools for both basic and translational research.
Zika; Drug discovery; Replicon; Flavivirus
Citation: Xuping Xie, Jing Zou, Chao Shan, Yujiao Yang, Dieudonné Buh Kum, Kai Dallmeier, Johan Neyts, Pei-Yong Shi Zika Virus Replicons For Drug Discovery http://dx.doi.org/10.1016/j.ebiom.2016.09.013
Received: 31 August 2016, Revised: 9 September 2016, Accepted: 13 September 2016, Available online: 14 September 2016
Copyright: © 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
X.X. was awarded with a postdoctoral fellowship from Novartis Institutes for BioMedical Research. P.Y.S. was supported by University of Texas Medical Branch startup award, University of Texas STARs Award, and NIH grant R01AI087856.
Conflict of Interest Statement
The authors have no conflict of interest in this study.
X.X., J.Z., S.C., Y.Y., and D.B.K. performed experiments and data analysis. X.X, K.D., J.N., and P.Y.S. interpreted the results. X.X., K.D., J.N., and P.Y.S. wrote the manuscript.
We thank our lab members and colleagues at University of Texas Medical Branch at Galveston for helpful discussions during the course of this study.