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

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

doi:10.1016/j.chom.2016.05.004

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

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

Research output: Contribution to journal › Article › peer-review

217 Scopus citations

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.

Original language	English (US)
Pages (from-to)	891-900
Number of pages	10
Journal	Cell Host and Microbe
Volume	19
Issue number	6
DOIs	https://doi.org/10.1016/j.chom.2016.05.004
State	Published - Jun 8 2016

Keywords

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

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2016.05.004

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Shan, C., Xie, X., Muruato, A. E., Rossi, S. L., Roundy, C. M., Azar, S. R., Yang, Y., Tesh, R. B., Bourne, N., Barrett, A. D., Vasilakis, N., Weaver, S. C., & Shi, P. Y. (2016). An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors. Cell Host and Microbe, 19(6), 891-900. https://doi.org/10.1016/j.chom.2016.05.004

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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.",

keywords = "Zika virus, antiviral drug discovery, flavivirus, genetic system, mosquito transmission, viral virulence",

author = "Chao Shan and Xuping Xie and Muruato, {Antonio E.} and Rossi, {Shannan L.} and Roundy, {Christopher M.} and Azar, {Sasha R.} and Yujiao Yang and Tesh, {Robert B.} and Nigel Bourne and Barrett, {Alan D.} and Nikos Vasilakis and Weaver, {Scott C.} and Shi, {Pei Yong}",

note = "Funding Information: We are grateful to Mariano A. Garcia-Blanco, Shelton S. Brarick, and their lab members for providing lab space, equipment, and helpful discussions during the course of this work. We thank James C. Lee, Shirley J. Broz, Lisa M. Pipper, and Julia K. Melchor for their support during the establishment of P.-Y.S.{\textquoteright}s lab at UTMB. This research was supported by NIH grants AI120942 and AI087856. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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doi = "10.1016/j.chom.2016.05.004",

language = "English (US)",

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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

N1 - Funding Information: We are grateful to Mariano A. Garcia-Blanco, Shelton S. Brarick, and their lab members for providing lab space, equipment, and helpful discussions during the course of this work. We thank James C. Lee, Shirley J. Broz, Lisa M. Pipper, and Julia K. Melchor for their support during the establishment of P.-Y.S.’s lab at UTMB. This research was supported by NIH grants AI120942 and AI087856. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/6/8

Y1 - 2016/6/8

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.

AB - 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.

KW - Zika virus

KW - antiviral drug discovery

KW - flavivirus

KW - genetic system

KW - mosquito transmission

KW - viral virulence

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

Abstract

Keywords

ASJC Scopus subject areas

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