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

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

Author information

1
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
2
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX 77555, USA.
3
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA.
4
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
5
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA.
6
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
7
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: peshi@utmb.edu.

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.

KEYWORDS:

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

PMID:
27198478
PMCID:
PMC5206987
DOI:
10.1016/j.chom.2016.05.004
[Indexed for MEDLINE]
Free PMC Article

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