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

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.

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  • Authors+Show Affiliations

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    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.

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    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.

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    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.

    ,

    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.

    ,

    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.

    ,

    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 Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.

    ,

    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.

    ,

    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.

    ,

    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.

    ,

    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.

    ,

    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.

    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.

    Source

    Cell host & microbe 19:6 2016 Jun 08 pg 891-900

    MeSH

    Animals
    Antiviral Agents
    Cell Line
    Cercopithecus aethiops
    DNA, Complementary
    Disease Models, Animal
    Drug Evaluation, Preclinical
    Mice
    Mosquito Vectors
    RNA, Viral
    Sequence Analysis, DNA
    Vero Cells
    Viral Vaccines
    Virulence
    Zika Virus
    Zika Virus Infection

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    27198478

    Citation

    Shan, Chao, et al. "An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors." Cell Host & Microbe, vol. 19, no. 6, 2016, pp. 891-900.
    Shan C, Xie X, Muruato AE, et al. An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors. Cell Host Microbe. 2016;19(6):891-900.
    Shan, C., Xie, X., Muruato, A. E., Rossi, S. L., Roundy, C. M., Azar, S. R., ... Shi, P. Y. (2016). An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors. Cell Host & Microbe, 19(6), pp. 891-900. doi:10.1016/j.chom.2016.05.004.
    Shan C, et al. 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. PubMed PMID: 27198478.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors. AU - Shan,Chao, AU - Xie,Xuping, AU - Muruato,Antonio E, AU - Rossi,Shannan L, AU - Roundy,Christopher M, AU - Azar,Sasha R, AU - Yang,Yujiao, AU - Tesh,Robert B, AU - Bourne,Nigel, AU - Barrett,Alan D, AU - Vasilakis,Nikos, AU - Weaver,Scott C, AU - Shi,Pei-Yong, Y1 - 2016/05/16/ PY - 2016/04/14/received PY - 2016/05/04/revised PY - 2016/05/05/accepted PY - 2016/5/21/entrez PY - 2016/5/21/pubmed PY - 2017/9/22/medline KW - Zika virus KW - antiviral drug discovery KW - flavivirus KW - genetic system KW - mosquito transmission KW - viral virulence SP - 891 EP - 900 JF - Cell host & microbe JO - Cell Host Microbe VL - 19 IS - 6 N2 - 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. SN - 1934-6069 UR - https://www.unboundmedicine.com/medline/citation/27198478/An_Infectious_cDNA_Clone_of_Zika_Virus_to_Study_Viral_Virulence_Mosquito_Transmission_and_Antiviral_Inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-3128(16)30200-1 DB - PRIME DP - Unbound Medicine ER -