An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors
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 th...
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| Veröffentlicht in: | Cell host & microbe 2016-06, Vol.19 (6), p.891-900 |
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| creator | Shan, Chao Xie, Xuping Muruato, Antonio E. Rossi, Shannan L. Roundy, Christopher M. Azar, Sasha R. Yang, Yujiao Tesh, Robert B. Bourne, Nigel Barrett, Alan D. Vasilakis, Nikos Weaver, Scott C. Shi, Pei-Yong |
| description | 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.
[Display omitted]
•An infectious cDNA clone of Zika virus and a luciferase reporter virus were developed•Recombinant Zika virus is virulent in A129 and AG129 mice•Recombinant Zika virus is highly infectious for Aedes aegypti mosquitos•The luciferase Zika virus can be used for antiviral drug discovery
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. |
| doi_str_mv | 10.1016/j.chom.2016.05.004 |
| format | Article |
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[Display omitted]
•An infectious cDNA clone of Zika virus and a luciferase reporter virus were developed•Recombinant Zika virus is virulent in A129 and AG129 mice•Recombinant Zika virus is highly infectious for Aedes aegypti mosquitos•The luciferase Zika virus can be used for antiviral drug discovery
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.</description><identifier>ISSN: 1931-3128</identifier><identifier>EISSN: 1934-6069</identifier><identifier>DOI: 10.1016/j.chom.2016.05.004</identifier><identifier>PMID: 27198478</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antiviral Agents - pharmacology ; antiviral drug discovery ; Cell Line ; Chlorocebus aethiops ; Disease Models, Animal ; DNA, Complementary - genetics ; DNA, Complementary - isolation & purification ; Drug Evaluation, Preclinical - methods ; flavivirus ; genetic system ; Mice ; mosquito transmission ; Mosquito Vectors - virology ; RNA, Viral - genetics ; RNA, Viral - isolation & purification ; Sequence Analysis, DNA ; Vero Cells ; Viral Vaccines - pharmacology ; viral virulence ; Virulence ; Zika virus ; Zika Virus - drug effects ; Zika Virus - genetics ; Zika Virus - pathogenicity ; Zika Virus Infection - transmission ; Zika Virus Infection - virology</subject><ispartof>Cell host & microbe, 2016-06, Vol.19 (6), p.891-900</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-207d40d62f2ae12ba27850d85cbe69e70417aabfc5db19f940aa4d3793ad3923</citedby><cites>FETCH-LOGICAL-c521t-207d40d62f2ae12ba27850d85cbe69e70417aabfc5db19f940aa4d3793ad3923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1931312816302001$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27198478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shan, Chao</creatorcontrib><creatorcontrib>Xie, Xuping</creatorcontrib><creatorcontrib>Muruato, Antonio E.</creatorcontrib><creatorcontrib>Rossi, Shannan L.</creatorcontrib><creatorcontrib>Roundy, Christopher M.</creatorcontrib><creatorcontrib>Azar, Sasha R.</creatorcontrib><creatorcontrib>Yang, Yujiao</creatorcontrib><creatorcontrib>Tesh, Robert B.</creatorcontrib><creatorcontrib>Bourne, Nigel</creatorcontrib><creatorcontrib>Barrett, Alan D.</creatorcontrib><creatorcontrib>Vasilakis, Nikos</creatorcontrib><creatorcontrib>Weaver, Scott C.</creatorcontrib><creatorcontrib>Shi, Pei-Yong</creatorcontrib><title>An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors</title><title>Cell host & microbe</title><addtitle>Cell Host Microbe</addtitle><description>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.
[Display omitted]
•An infectious cDNA clone of Zika virus and a luciferase reporter virus were developed•Recombinant Zika virus is virulent in A129 and AG129 mice•Recombinant Zika virus is highly infectious for Aedes aegypti mosquitos•The luciferase Zika virus can be used for antiviral drug discovery
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.</description><subject>Animals</subject><subject>Antiviral Agents - pharmacology</subject><subject>antiviral drug discovery</subject><subject>Cell Line</subject><subject>Chlorocebus aethiops</subject><subject>Disease Models, Animal</subject><subject>DNA, Complementary - genetics</subject><subject>DNA, Complementary - isolation & purification</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>flavivirus</subject><subject>genetic system</subject><subject>Mice</subject><subject>mosquito transmission</subject><subject>Mosquito Vectors - virology</subject><subject>RNA, Viral - genetics</subject><subject>RNA, Viral - isolation & purification</subject><subject>Sequence Analysis, DNA</subject><subject>Vero Cells</subject><subject>Viral Vaccines - pharmacology</subject><subject>viral virulence</subject><subject>Virulence</subject><subject>Zika virus</subject><subject>Zika Virus - drug effects</subject><subject>Zika Virus - genetics</subject><subject>Zika Virus - pathogenicity</subject><subject>Zika Virus Infection - transmission</subject><subject>Zika Virus Infection - virology</subject><issn>1931-3128</issn><issn>1934-6069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1OAyEUhYnRWP9ewIXhAZwRmGGYSYxJU_-aVF3YuHBDGGAstYUK0ya-vUyrjW5cceGcey58AHCKUYoRLi6mqZy4eUpinSKaIpTvgANcZXlSoKLaXdc4yTApe-AwhClClCKG90GPMFyVOSsPwKJv4dA2WrbGLQOU1499OJg5q6Fr4Kt5F_DF-Ci0Dj63S_XZbcVsfTjTVupz-ODCx9JEfeyFDXMTgnH2HAqrYN-2ZrX2D-3E1NHkwzHYa8Qs6JPv9QiMb2_Gg_tk9HQ3HPRHiaQEtwlBTOVIFaQhQmNSC8JKilRJZa2LSjOUYyZE3Uiqalw1VY6EyFXGqkyorCLZEbjaxC6W9VwrqW0b78EX3syF_-ROGP5XsWbC39yKUxLZlSwGkE2A9C4Er5ttL0a8w8-nvMPPO_wcUR7xx6az31O3LT-8o-FyY9Dx6SujPQ_SdByV8fEPuHLmv_wvJIqZDw</recordid><startdate>20160608</startdate><enddate>20160608</enddate><creator>Shan, Chao</creator><creator>Xie, Xuping</creator><creator>Muruato, Antonio E.</creator><creator>Rossi, Shannan L.</creator><creator>Roundy, Christopher M.</creator><creator>Azar, Sasha R.</creator><creator>Yang, Yujiao</creator><creator>Tesh, Robert B.</creator><creator>Bourne, Nigel</creator><creator>Barrett, Alan D.</creator><creator>Vasilakis, Nikos</creator><creator>Weaver, Scott C.</creator><creator>Shi, Pei-Yong</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20160608</creationdate><title>An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors</title><author>Shan, Chao ; 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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.
[Display omitted]
•An infectious cDNA clone of Zika virus and a luciferase reporter virus were developed•Recombinant Zika virus is virulent in A129 and AG129 mice•Recombinant Zika virus is highly infectious for Aedes aegypti mosquitos•The luciferase Zika virus can be used for antiviral drug discovery
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27198478</pmid><doi>10.1016/j.chom.2016.05.004</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell host & microbe, 2016-06, Vol.19 (6), p.891-900 |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antiviral Agents - pharmacology antiviral drug discovery Cell Line Chlorocebus aethiops Disease Models, Animal DNA, Complementary - genetics DNA, Complementary - isolation & purification Drug Evaluation, Preclinical - methods flavivirus genetic system Mice mosquito transmission Mosquito Vectors - virology RNA, Viral - genetics RNA, Viral - isolation & purification Sequence Analysis, DNA Vero Cells Viral Vaccines - pharmacology viral virulence Virulence Zika virus Zika Virus - drug effects Zika Virus - genetics Zika Virus - pathogenicity Zika Virus Infection - transmission Zika Virus Infection - virology |
| title | An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors |
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