<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case

ABSTRACT Zika virus (ZIKV) has recently emerged and is the etiological agent of congenital Zika syndrome (CZS), a spectrum of congenital abnormalities arising from neural tissue infections in utero. Herein, we describe the de novo generation of a new ZIKV isolate, ZIKVNatal, using a modified circula...

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Autores principales:	Yin Xiang Setoh, Natalie A. Prow, Nias Peng, Leon E. Hugo, Gregor Devine, Jessamine E. Hazlewood, Andreas Suhrbier, Alexander A. Khromykh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	infectious DNA Zika virus flavivirus mouse model Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ee4845118f824c419bcc0f43801b762a
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spelling	oai:doaj.org-article:ee4845118f824c419bcc0f43801b762a2021-11-15T15:21:47Z<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case10.1128/mSphereDirect.00190-172379-5042https://doaj.org/article/ee4845118f824c419bcc0f43801b762a2017-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00190-17https://doaj.org/toc/2379-5042ABSTRACT Zika virus (ZIKV) has recently emerged and is the etiological agent of congenital Zika syndrome (CZS), a spectrum of congenital abnormalities arising from neural tissue infections in utero. Herein, we describe the de novo generation of a new ZIKV isolate, ZIKVNatal, using a modified circular polymerase extension reaction protocol and sequence data obtained from a ZIKV-infected fetus with microcephaly. ZIKVNatal thus has no laboratory passage history and is unequivocally associated with CZS. ZIKVNatal could be used to establish a fetal brain infection model in IFNAR−/− mice (including intrauterine growth restriction) without causing symptomatic infections in dams. ZIKVNatal was also able to be transmitted by Aedes aegypti mosquitoes. ZIKVNatal thus retains key aspects of circulating pathogenic ZIKVs and illustrates a novel methodology for obtaining an authentic functional viral isolate by using data from deep sequencing of infected tissues. IMPORTANCE The major complications of an ongoing Zika virus outbreak in the Americas and Asia are congenital defects caused by the virus’s ability to cross the placenta and infect the fetal brain. The ability to generate molecular tools to analyze viral isolates from the current outbreak is essential for furthering our understanding of how these viruses cause congenital defects. The majority of existing viral isolates and infectious cDNA clones generated from them have undergone various numbers of passages in cell culture and/or suckling mice, which is likely to result in the accumulation of adaptive mutations that may affect viral properties. The approach described herein allows rapid generation of new, fully functional Zika virus isolates directly from deep sequencing data from virus-infected tissues without the need for prior virus passaging and for the generation and propagation of full-length cDNA clones. The approach should be applicable to other medically important flaviviruses and perhaps other positive-strand RNA viruses.Yin Xiang SetohNatalie A. ProwNias PengLeon E. HugoGregor DevineJessamine E. HazlewoodAndreas SuhrbierAlexander A. KhromykhAmerican Society for Microbiologyarticleinfectious DNAZika virusflavivirusmouse modelMicrobiologyQR1-502ENmSphere, Vol 2, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	infectious DNA Zika virus flavivirus mouse model Microbiology QR1-502
spellingShingle	infectious DNA Zika virus flavivirus mouse model Microbiology QR1-502 Yin Xiang Setoh Natalie A. Prow Nias Peng Leon E. Hugo Gregor Devine Jessamine E. Hazlewood Andreas Suhrbier Alexander A. Khromykh <italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case
description	ABSTRACT Zika virus (ZIKV) has recently emerged and is the etiological agent of congenital Zika syndrome (CZS), a spectrum of congenital abnormalities arising from neural tissue infections in utero. Herein, we describe the de novo generation of a new ZIKV isolate, ZIKVNatal, using a modified circular polymerase extension reaction protocol and sequence data obtained from a ZIKV-infected fetus with microcephaly. ZIKVNatal thus has no laboratory passage history and is unequivocally associated with CZS. ZIKVNatal could be used to establish a fetal brain infection model in IFNAR−/− mice (including intrauterine growth restriction) without causing symptomatic infections in dams. ZIKVNatal was also able to be transmitted by Aedes aegypti mosquitoes. ZIKVNatal thus retains key aspects of circulating pathogenic ZIKVs and illustrates a novel methodology for obtaining an authentic functional viral isolate by using data from deep sequencing of infected tissues. IMPORTANCE The major complications of an ongoing Zika virus outbreak in the Americas and Asia are congenital defects caused by the virus’s ability to cross the placenta and infect the fetal brain. The ability to generate molecular tools to analyze viral isolates from the current outbreak is essential for furthering our understanding of how these viruses cause congenital defects. The majority of existing viral isolates and infectious cDNA clones generated from them have undergone various numbers of passages in cell culture and/or suckling mice, which is likely to result in the accumulation of adaptive mutations that may affect viral properties. The approach described herein allows rapid generation of new, fully functional Zika virus isolates directly from deep sequencing data from virus-infected tissues without the need for prior virus passaging and for the generation and propagation of full-length cDNA clones. The approach should be applicable to other medically important flaviviruses and perhaps other positive-strand RNA viruses.
format	article
author	Yin Xiang Setoh Natalie A. Prow Nias Peng Leon E. Hugo Gregor Devine Jessamine E. Hazlewood Andreas Suhrbier Alexander A. Khromykh
author_facet	Yin Xiang Setoh Natalie A. Prow Nias Peng Leon E. Hugo Gregor Devine Jessamine E. Hazlewood Andreas Suhrbier Alexander A. Khromykh
author_sort	Yin Xiang Setoh
title	<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case
title_short	<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case
title_full	<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case
title_fullStr	<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case
title_full_unstemmed	<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case
title_sort	<italic toggle="yes">de novo</italic> generation and characterization of new zika virus isolate using sequence data from a microcephaly case
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/ee4845118f824c419bcc0f43801b762a
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<italic toggle="yes">De Novo</italic> Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case

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