An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection

An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection

Abstract Machupo virus (MACV) is a New World (NW) arenavirus and causative agent of Bolivian hemorrhagic fever (HF). Here, we identified a variant of MACV strain Carvallo termed Car91 that was attenuated in guinea pigs. Infection of guinea pigs with an earlier passage of Carvallo, termed Car68, resu...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Joseph W. Golden, Brett Beitzel, Jason T. Ladner, Eric M. Mucker, Steven A. Kwilas, Gustavo Palacios, Jay W. Hooper
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/4f7b5bc0b3ea44f68846a16a888e462d
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:4f7b5bc0b3ea44f68846a16a888e462d
record_format dspace
spelling oai:doaj.org-article:4f7b5bc0b3ea44f68846a16a888e462d2021-12-02T16:06:03ZAn attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection10.1038/s41598-017-04889-x2045-2322https://doaj.org/article/4f7b5bc0b3ea44f68846a16a888e462d2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04889-xhttps://doaj.org/toc/2045-2322Abstract Machupo virus (MACV) is a New World (NW) arenavirus and causative agent of Bolivian hemorrhagic fever (HF). Here, we identified a variant of MACV strain Carvallo termed Car91 that was attenuated in guinea pigs. Infection of guinea pigs with an earlier passage of Carvallo, termed Car68, resulted in a lethal disease with a 63% mortality rate. Sequencing analysis revealed that compared to Car68, Car91 had a 35 nucleotide (nt) deletion and a point mutation within the L-segment intergenic region (IGR), and three silent changes in the polymerase gene that did not impact amino acid coding. No changes were found on the S-segment. Because it was apathogenic, we determined if Car91 could protect guinea pigs against Guanarito virus (GTOV), a distantly related NW arenavirus. While naïve animals succumbed to GTOV infection, 88% of the Car91-exposed guinea pigs were protected. These findings indicate that attenuated MACV vaccines can provide heterologous protection against NW arenaviruses. The disruption in the L-segment IGR, including a single point mutant and 35 nt partial deletion, were the only major variance detected between virulent and avirulent isolates, implicating its role in attenuation. Overall, our data support the development of live-attenuated arenaviruses as broadly protective pan-arenavirus vaccines.Joseph W. GoldenBrett BeitzelJason T. LadnerEric M. MuckerSteven A. KwilasGustavo PalaciosJay W. HooperNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Joseph W. Golden
Brett Beitzel
Jason T. Ladner
Eric M. Mucker
Steven A. Kwilas
Gustavo Palacios
Jay W. Hooper
An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection
description Abstract Machupo virus (MACV) is a New World (NW) arenavirus and causative agent of Bolivian hemorrhagic fever (HF). Here, we identified a variant of MACV strain Carvallo termed Car91 that was attenuated in guinea pigs. Infection of guinea pigs with an earlier passage of Carvallo, termed Car68, resulted in a lethal disease with a 63% mortality rate. Sequencing analysis revealed that compared to Car68, Car91 had a 35 nucleotide (nt) deletion and a point mutation within the L-segment intergenic region (IGR), and three silent changes in the polymerase gene that did not impact amino acid coding. No changes were found on the S-segment. Because it was apathogenic, we determined if Car91 could protect guinea pigs against Guanarito virus (GTOV), a distantly related NW arenavirus. While naïve animals succumbed to GTOV infection, 88% of the Car91-exposed guinea pigs were protected. These findings indicate that attenuated MACV vaccines can provide heterologous protection against NW arenaviruses. The disruption in the L-segment IGR, including a single point mutant and 35 nt partial deletion, were the only major variance detected between virulent and avirulent isolates, implicating its role in attenuation. Overall, our data support the development of live-attenuated arenaviruses as broadly protective pan-arenavirus vaccines.
format article
author Joseph W. Golden
Brett Beitzel
Jason T. Ladner
Eric M. Mucker
Steven A. Kwilas
Gustavo Palacios
Jay W. Hooper
author_facet Joseph W. Golden
Brett Beitzel
Jason T. Ladner
Eric M. Mucker
Steven A. Kwilas
Gustavo Palacios
Jay W. Hooper
author_sort Joseph W. Golden
title An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection
title_short An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection
title_full An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection
title_fullStr An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection
title_full_unstemmed An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection
title_sort attenuated machupo virus with a disrupted l-segment intergenic region protects guinea pigs against lethal guanarito virus infection
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/4f7b5bc0b3ea44f68846a16a888e462d
work_keys_str_mv AT josephwgolden anattenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT brettbeitzel anattenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT jasontladner anattenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT ericmmucker anattenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT stevenakwilas anattenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT gustavopalacios anattenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT jaywhooper anattenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT josephwgolden attenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT brettbeitzel attenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT jasontladner attenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT ericmmucker attenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT stevenakwilas attenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT gustavopalacios attenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
AT jaywhooper attenuatedmachupoviruswithadisruptedlsegmentintergenicregionprotectsguineapigsagainstlethalguanaritovirusinfection
_version_ 1718385145872908288

Ejemplares similares