A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers

A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers

Centro de Investigación en Sanidad Animal (CISA)

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Bibliographic Details
Main Authors: Borrego, Belén, Brun Torres, Alejandro
Other Authors: Comunidad de Madrid
Format: artículo biblioteca
Language:English
Published: Frontiers Media 2021-02-09
Subjects:Rift Valley fever virus, Favipiravir, Live attenuated vaccines, Mutagenesis, Virulence markers,
Online Access:http://hdl.handle.net/10261/275409
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100012818
https://api.elsevier.com/content/abstract/scopus_id/85101195431
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spelling dig-inia-es-10261-2754092024-05-18T20:36:30Z A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers Borrego, Belén Brun Torres, Alejandro Comunidad de Madrid Ministerio de Ciencia e Innovación (España) Borrego, Belén [0000-0002-0801-9166] Brun, Alejandro [0000-0001-7865-538X] Rift Valley fever virus Favipiravir Live attenuated vaccines Mutagenesis Virulence markers Centro de Investigación en Sanidad Animal (CISA) Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes Rift Valley fever (RVF), a zoonotic disease of wild and domestic ruminants, causing serious economic losses and a threat to human health that could be controlled by vaccination. Though RVF vaccines are available for livestock, no RVF vaccines have been licensed for veterinary use in non-endemic countries nor for human populations in RVF risk areas. In a recent work, we showed that favipiravir, a promising drug with antiviral activity against a number of RNA viruses, led to the extinction of RVFV from infected cell cultures. Nevertheless, certain drug concentrations allowed the recovery of a virus variant showing increased resistance to favipiravir. In this work, we characterized this novel resistant variant both at genomic and phenotypic level in vitro and in vivo. Interestingly, the resistant virus displayed reduced growth rates in C6/36 insect cells but not in mammalian cell lines, and was highly attenuated but still immunogenic in vivo. Some amino acid substitutions were identified in the viral RNA-dependent RNA-polymerase (RdRp) gene and in the virus encoded type I-interferon (IFN-I) antagonist NSs gene, in catalytic core motifs and nuclear localization associated positions, respectively. These data may help to characterize novel potential virulence markers, offering additional strategies for further safety improvements of RVF live attenuated vaccine candidates. This work was supported by Grants Nos. S2013/ABI-2906 (PLATESA) and P2018/BAA-4370 (PLATESA2) from Comunidad de Madrid/FEDER and AGL2017-83326-R from Ministerio de Ciencia e Innovación. The funders had no role in the design, and writing of the report and the decision to submit the article for publication. Peer reviewed 11 Pág. 2022-07-13T09:39:28Z 2022-07-13T09:39:28Z 2021-02-09 artículo http://purl.org/coar/resource_type/c_6501 Frontiers in Microbiology 11: 621463 (2021) 1664-302X http://hdl.handle.net/10261/275409 10.3389/fmicb.2020.621463 http://dx.doi.org/10.13039/501100004837 http://dx.doi.org/10.13039/100012818 33633696 2-s2.0-85101195431 https://api.elsevier.com/content/abstract/scopus_id/85101195431 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# S2013/ABI-2906/PLATESA S2018/BAA-4370/PLATESA2 info:eu-repo/grantAgreement/MICINN//AGL2017-83326-R Frontiers in microbiology Publisher's version https://doi.org/10.3389/fmicb.2020.621463 Sí open Frontiers Media
institution INIA ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-inia-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del INIA España
language English
topic Rift Valley fever virus
Favipiravir
Live attenuated vaccines
Mutagenesis
Virulence markers
Rift Valley fever virus
Favipiravir
Live attenuated vaccines
Mutagenesis
Virulence markers
spellingShingle Rift Valley fever virus
Favipiravir
Live attenuated vaccines
Mutagenesis
Virulence markers
Rift Valley fever virus
Favipiravir
Live attenuated vaccines
Mutagenesis
Virulence markers
Borrego, Belén
Brun Torres, Alejandro
A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers
description Centro de Investigación en Sanidad Animal (CISA)
author2 Comunidad de Madrid
author_facet Comunidad de Madrid
Borrego, Belén
Brun Torres, Alejandro
format artículo
topic_facet Rift Valley fever virus
Favipiravir
Live attenuated vaccines
Mutagenesis
Virulence markers
author Borrego, Belén
Brun Torres, Alejandro
author_sort Borrego, Belén
title A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers
title_short A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers
title_full A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers
title_fullStr A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers
title_full_unstemmed A Hyper-Attenuated Variant of Rift Valley Fever Virus Generated by a Mutagenic Drug (Favipiravir) Unveils Potential Virulence Markers
title_sort hyper-attenuated variant of rift valley fever virus generated by a mutagenic drug (favipiravir) unveils potential virulence markers
publisher Frontiers Media
publishDate 2021-02-09
url http://hdl.handle.net/10261/275409
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100012818
https://api.elsevier.com/content/abstract/scopus_id/85101195431
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