In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model

West Nile virus (WNV) strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage...

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Autores principales: Szentpáli-Gavallér, Katalin, Lim, Stephanie M., Dencső, László, Bányai, Krisztián, Koraka, Penelope, Osterhaus, Albert D.M.E., Martina, Byron E.E., Bakonyi, Tamás, Bálint, Ádám
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776204/
https://www.ncbi.nlm.nih.gov/pubmed/26907325
http://dx.doi.org/10.3390/v8020049
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author Szentpáli-Gavallér, Katalin
Lim, Stephanie M.
Dencső, László
Bányai, Krisztián
Koraka, Penelope
Osterhaus, Albert D.M.E.
Martina, Byron E.E.
Bakonyi, Tamás
Bálint, Ádám
author_facet Szentpáli-Gavallér, Katalin
Lim, Stephanie M.
Dencső, László
Bányai, Krisztián
Koraka, Penelope
Osterhaus, Albert D.M.E.
Martina, Byron E.E.
Bakonyi, Tamás
Bálint, Ádám
author_sort Szentpáli-Gavallér, Katalin
collection PubMed
description West Nile virus (WNV) strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage 2 strain (578/10; Central Europe) was generated and amino acid substitutions that have been shown to attenuate lineage 1 WNVs were introduced into the nonstructural proteins (NS1 (P250L), NS2A (A30P), NS3 (P249H) NS4B (P38G, C102S, E249G)). The mouse neuroinvasive phenotype of each mutant virus was examined following intraperitoneal inoculation of C57BL/6 mice. Only the NS1-P250L mutation was associated with a significant attenuation of virulence in mice compared to the wild-type. Multiplication kinetics in cell culture revealed significantly lower infectious virus titres for the NS1 mutant compared to the wild-type, as well as significantly lower amounts of positive and negative stranded RNA.
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spelling pubmed-47762042016-03-09 In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model Szentpáli-Gavallér, Katalin Lim, Stephanie M. Dencső, László Bányai, Krisztián Koraka, Penelope Osterhaus, Albert D.M.E. Martina, Byron E.E. Bakonyi, Tamás Bálint, Ádám Viruses Article West Nile virus (WNV) strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage 2 strain (578/10; Central Europe) was generated and amino acid substitutions that have been shown to attenuate lineage 1 WNVs were introduced into the nonstructural proteins (NS1 (P250L), NS2A (A30P), NS3 (P249H) NS4B (P38G, C102S, E249G)). The mouse neuroinvasive phenotype of each mutant virus was examined following intraperitoneal inoculation of C57BL/6 mice. Only the NS1-P250L mutation was associated with a significant attenuation of virulence in mice compared to the wild-type. Multiplication kinetics in cell culture revealed significantly lower infectious virus titres for the NS1 mutant compared to the wild-type, as well as significantly lower amounts of positive and negative stranded RNA. MDPI 2016-02-19 /pmc/articles/PMC4776204/ /pubmed/26907325 http://dx.doi.org/10.3390/v8020049 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szentpáli-Gavallér, Katalin
Lim, Stephanie M.
Dencső, László
Bányai, Krisztián
Koraka, Penelope
Osterhaus, Albert D.M.E.
Martina, Byron E.E.
Bakonyi, Tamás
Bálint, Ádám
In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model
title In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model
title_full In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model
title_fullStr In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model
title_full_unstemmed In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model
title_short In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model
title_sort in vitro and in vivo evaluation of mutations in the ns region of lineage 2 west nile virus associated with neuroinvasiveness in a mammalian model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776204/
https://www.ncbi.nlm.nih.gov/pubmed/26907325
http://dx.doi.org/10.3390/v8020049
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