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

Chao Shan, Xuping Xie, Antonio E. Muruato, Shannan Rossi, Christopher M. Roundy, Sasha R. Azar, Yujiao Yang, Robert B. Tesh, Nigel Bourne, Alan Barrett, Nikos Vasilakis, Scott Weaver, Pei-Yong Shi

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

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. Zika virus (ZIKV) is causing devastating epidemics with severe disease. Shan et al. generated an infectious cDNA clone of ZIKV as well as a luciferase reporter virus. Recombinant ZIKV is virulent in mice and infectious in Aedes aegypti and thus may help identify viral determinants of virulence and transmission.

Original languageEnglish (US)
JournalCell Host and Microbe
DOIs
StateAccepted/In press - Apr 14 2016

Fingerprint

Culicidae
Antiviral Agents
Virulence
Complementary DNA
Clone Cells
Aedes
Viruses
Luciferases
Zika Virus
Reverse Genetics
Virus Diseases
Vaccines
RNA
Infection

Keywords

  • Antiviral drug discovery
  • Flavivirus
  • Genetic system
  • Mosquito transmission
  • Viral virulence
  • Zika virus

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors. / Shan, Chao; Xie, Xuping; Muruato, Antonio E.; Rossi, Shannan; Roundy, Christopher M.; Azar, Sasha R.; Yang, Yujiao; Tesh, Robert B.; Bourne, Nigel; Barrett, Alan; Vasilakis, Nikos; Weaver, Scott; Shi, Pei-Yong.

In: Cell Host and Microbe, 14.04.2016.

Research output: Contribution to journalArticle

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