title: Zika Virus Replicons for Drug Discovery.
abstract: 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.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Xuping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Shan
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; College of Animal Science and Technology, Southwest University, Chongqing, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium.
authors.forename: Dieudonné Buh
authors.initials: DB
authors.lastname: Kum
authors.affiliation: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium.
authors.forename: Kai
authors.initials: K
authors.lastname: Dallmeier
authors.affiliation: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Pharmacology & Toxicology, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015870:Gene Expression; D017930:Genes, Reporter; D016679:Genome, Viral; D006801:Humans; D012093:Replicon; D014779:Virus Replication / Q000187:drug effects*; D000071244:Zika Virus / Q000187:drug effects* / Q000502:physiology*; D000071243:Zika Virus Infection / Q000188:drug therapy / Q000821:virology
chemical_list: D000998:Antiviral Agents
keywords: Drug discovery; Flavivirus; Replicon; Zika