title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Shan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Xuping
authors.initials: X
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Muruato
authors.affiliation: 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.
authors.forename: Shannan L
authors.initials: SL
authors.lastname: Rossi
authors.affiliation: 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.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Roundy
authors.affiliation: 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.
authors.forename: Sasha R
authors.initials: SR
authors.lastname: Azar
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Tesh
authors.affiliation: 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.
authors.forename: Nigel
authors.initials: N
authors.lastname: Bourne
authors.affiliation: 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.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Barrett
authors.affiliation: 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.
authors.forename: Nikos
authors.initials: N
authors.lastname: Vasilakis
authors.affiliation: 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.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.affiliation: 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.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics* / Q000302:isolation & purification; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D051379:Mice; D000072138:Mosquito Vectors / Q000821:virology; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA; D014709:Vero Cells; D014765:Viral Vaccines / Q000494:pharmacology; D014774:Virulence; D000071244:Zika Virus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D000071243:Zika Virus Infection / Q000635:transmission* / Q000821:virology
chemical_list: D000998:Antiviral Agents; D018076:DNA, Complementary; D012367:RNA, Viral; D014765:Viral Vaccines
keywords: Zika virus; antiviral drug discovery; flavivirus; genetic system; mosquito transmission; viral virulence