An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors

Cell Host Microbe. 2016 Jun 8;19(6):891-900. doi: 10.1016/j.chom.2016.05.004. Epub 2016 May 16.


The Asian lineage of Zika virus (ZIKV) has recently caused epidemics and severe disease. Unraveling the mechanisms causing increased viral transmissibility and disease severity requires experimental systems. We report an infectious cDNA clone of ZIKV that was generated using a clinical isolate of the Asian lineage. The cDNA clone-derived RNA is infectious in cells, generating recombinant ZIKV. The recombinant virus is virulent in established ZIKV mouse models, leading to neurological signs relevant to human disease. Additionally, recombinant ZIKV is infectious for Aedes aegypti and thus provides a means to examine virus transmission. The infectious cDNA clone was further used to generate a luciferase ZIKV that exhibited sensitivity to a panflavivirus inhibitor, highlighting its potential utility for antiviral screening. This ZIKV reverse genetic system, together with mouse and mosquito infection models, may help identify viral determinants of human virulence and mosquito transmission as well as inform vaccine and therapeutic strategies.

Keywords: Zika virus; antiviral drug discovery; flavivirus; genetic system; mosquito transmission; viral virulence.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Chlorocebus aethiops
  • DNA, Complementary / genetics*
  • DNA, Complementary / isolation & purification
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Mice
  • Mosquito Vectors / virology
  • RNA, Viral / genetics
  • RNA, Viral / isolation & purification*
  • Sequence Analysis, DNA
  • Vero Cells
  • Viral Vaccines / pharmacology
  • Virulence
  • Zika Virus / drug effects
  • Zika Virus / genetics*
  • Zika Virus / pathogenicity
  • Zika Virus Infection / transmission*
  • Zika Virus Infection / virology


  • Antiviral Agents
  • DNA, Complementary
  • RNA, Viral
  • Viral Vaccines