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The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore, it is considered a major threat to both human and animal health. In a previous work, we described a nov...

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Autores principales: Borrego, Belén, Moreno, Sandra, de la Losa, Nuria, Weber, Friedemann, Brun, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064099/
https://www.ncbi.nlm.nih.gov/pubmed/33805122
http://dx.doi.org/10.3390/v13040542
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author Borrego, Belén
Moreno, Sandra
de la Losa, Nuria
Weber, Friedemann
Brun, Alejandro
author_facet Borrego, Belén
Moreno, Sandra
de la Losa, Nuria
Weber, Friedemann
Brun, Alejandro
author_sort Borrego, Belén
collection PubMed
description Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore, it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an interferon (IFN)-competent cell line as well as the production of interferon beta (IFN-β) did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results highlight the key role of the NSs protein in the modulation of viral infectivity.
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spelling pubmed-80640992021-04-24 The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice Borrego, Belén Moreno, Sandra de la Losa, Nuria Weber, Friedemann Brun, Alejandro Viruses Article Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore, it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an interferon (IFN)-competent cell line as well as the production of interferon beta (IFN-β) did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results highlight the key role of the NSs protein in the modulation of viral infectivity. MDPI 2021-03-24 /pmc/articles/PMC8064099/ /pubmed/33805122 http://dx.doi.org/10.3390/v13040542 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Borrego, Belén
Moreno, Sandra
de la Losa, Nuria
Weber, Friedemann
Brun, Alejandro
The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice
title The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice
title_full The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice
title_fullStr The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice
title_full_unstemmed The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice
title_short The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice
title_sort change p82l in the rift valley fever virus nss protein confers attenuation in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064099/
https://www.ncbi.nlm.nih.gov/pubmed/33805122
http://dx.doi.org/10.3390/v13040542
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