Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time

Abstract Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. Th...

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Autores principales:	Haiyan Wei, Jonathan Audet, Gary Wong, Shihua He, Xueyong Huang, Todd Cutts, Steven Theriault, Bianli Xu, Gary Kobinger, Xiangguo Qiu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8796fb766a094b68a66bfa75e8854c8c
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spelling	oai:doaj.org-article:8796fb766a094b68a66bfa75e8854c8c2021-12-02T11:40:51ZDeep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time10.1038/s41598-017-03318-32045-2322https://doaj.org/article/8796fb766a094b68a66bfa75e8854c8c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03318-3https://doaj.org/toc/2045-2322Abstract Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. The mouse-adapted MARV exhibits many of the hallmarks of MARV disease in humans. By applying deep-sequencing to every passage of the virus, we are able to study virus evolution in this host with surprising precision. We show that two regions go through substantial changes: the intergenic region between NP and VP35, as well as the first 100 amino acids of the VP40 protein. Our results also reveal that there were profound changes during the production of the final virus stock in cell culture. Overall, our results show that a handful of regions carry most of the mutations acquired during the adaptation of the virus to a new host and that many mutations become fixed very early during the adaptation process.Haiyan WeiJonathan AudetGary WongShihua HeXueyong HuangTodd CuttsSteven TheriaultBianli XuGary KobingerXiangguo QiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Haiyan Wei Jonathan Audet Gary Wong Shihua He Xueyong Huang Todd Cutts Steven Theriault Bianli Xu Gary Kobinger Xiangguo Qiu Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time
description	Abstract Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. The mouse-adapted MARV exhibits many of the hallmarks of MARV disease in humans. By applying deep-sequencing to every passage of the virus, we are able to study virus evolution in this host with surprising precision. We show that two regions go through substantial changes: the intergenic region between NP and VP35, as well as the first 100 amino acids of the VP40 protein. Our results also reveal that there were profound changes during the production of the final virus stock in cell culture. Overall, our results show that a handful of regions carry most of the mutations acquired during the adaptation of the virus to a new host and that many mutations become fixed very early during the adaptation process.
format	article
author	Haiyan Wei Jonathan Audet Gary Wong Shihua He Xueyong Huang Todd Cutts Steven Theriault Bianli Xu Gary Kobinger Xiangguo Qiu
author_facet	Haiyan Wei Jonathan Audet Gary Wong Shihua He Xueyong Huang Todd Cutts Steven Theriault Bianli Xu Gary Kobinger Xiangguo Qiu
author_sort	Haiyan Wei
title	Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time
title_short	Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time
title_full	Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time
title_fullStr	Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time
title_full_unstemmed	Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time
title_sort	deep-sequencing of marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8796fb766a094b68a66bfa75e8854c8c
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Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time

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