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Maintenance of a host-specific minority mutation in the West Nile virus NS3

West Nile virus (WNV), the most prevalent arthropod-borne virus (arbovirus) in the United States, is maintained in a cycle between Culex spp. mosquitoes and birds. Arboviruses exist within hosts and vectors as a diverse set of closely related genotypes. In theory, this genetic diversity can facilita...

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Autores principales: Caldwell, Haley S., Kuo, Lili, Pata, Janice D., Dupuis, Alan P., Arnold, Jamie J., Yeager, Calvin, Stout, Jessica, Koetzner, Cheri A., Payne, Anne F., Bialosuknia, Sean M., Banker, Elyse M., Nolen, Taylor A., Cameron, Craig E., Ciota, Alexander T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10428113/
https://www.ncbi.nlm.nih.gov/pubmed/37593454
http://dx.doi.org/10.1016/j.isci.2023.107468
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author Caldwell, Haley S.
Kuo, Lili
Pata, Janice D.
Dupuis, Alan P.
Arnold, Jamie J.
Yeager, Calvin
Stout, Jessica
Koetzner, Cheri A.
Payne, Anne F.
Bialosuknia, Sean M.
Banker, Elyse M.
Nolen, Taylor A.
Cameron, Craig E.
Ciota, Alexander T.
author_facet Caldwell, Haley S.
Kuo, Lili
Pata, Janice D.
Dupuis, Alan P.
Arnold, Jamie J.
Yeager, Calvin
Stout, Jessica
Koetzner, Cheri A.
Payne, Anne F.
Bialosuknia, Sean M.
Banker, Elyse M.
Nolen, Taylor A.
Cameron, Craig E.
Ciota, Alexander T.
author_sort Caldwell, Haley S.
collection PubMed
description West Nile virus (WNV), the most prevalent arthropod-borne virus (arbovirus) in the United States, is maintained in a cycle between Culex spp. mosquitoes and birds. Arboviruses exist within hosts and vectors as a diverse set of closely related genotypes. In theory, this genetic diversity can facilitate adaptation to distinct environments during host cycling, yet host-specific fitness of minority genotypes has not been assessed. Utilizing WNV deep-sequencing data, we previously identified a naturally occurring, mosquito-biased substitution, NS3 P319L. Using both cell culture and experimental infection in natural hosts, we demonstrated that this substitution confers attenuation in vertebrate hosts and increased transmissibility by mosquitoes. Biochemical assays demonstrated temperature-sensitive ATPase activity consistent with host-specific phenotypes. Together these data confirm the maintenance of host-specific minority variants in arbovirus mutant swarms, suggest a unique role for NS3 in viral fitness, and demonstrate that intrahost sequence data can inform mechanisms of host-specific adaptation.
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spelling pubmed-104281132023-08-17 Maintenance of a host-specific minority mutation in the West Nile virus NS3 Caldwell, Haley S. Kuo, Lili Pata, Janice D. Dupuis, Alan P. Arnold, Jamie J. Yeager, Calvin Stout, Jessica Koetzner, Cheri A. Payne, Anne F. Bialosuknia, Sean M. Banker, Elyse M. Nolen, Taylor A. Cameron, Craig E. Ciota, Alexander T. iScience Article West Nile virus (WNV), the most prevalent arthropod-borne virus (arbovirus) in the United States, is maintained in a cycle between Culex spp. mosquitoes and birds. Arboviruses exist within hosts and vectors as a diverse set of closely related genotypes. In theory, this genetic diversity can facilitate adaptation to distinct environments during host cycling, yet host-specific fitness of minority genotypes has not been assessed. Utilizing WNV deep-sequencing data, we previously identified a naturally occurring, mosquito-biased substitution, NS3 P319L. Using both cell culture and experimental infection in natural hosts, we demonstrated that this substitution confers attenuation in vertebrate hosts and increased transmissibility by mosquitoes. Biochemical assays demonstrated temperature-sensitive ATPase activity consistent with host-specific phenotypes. Together these data confirm the maintenance of host-specific minority variants in arbovirus mutant swarms, suggest a unique role for NS3 in viral fitness, and demonstrate that intrahost sequence data can inform mechanisms of host-specific adaptation. Elsevier 2023-07-26 /pmc/articles/PMC10428113/ /pubmed/37593454 http://dx.doi.org/10.1016/j.isci.2023.107468 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Caldwell, Haley S.
Kuo, Lili
Pata, Janice D.
Dupuis, Alan P.
Arnold, Jamie J.
Yeager, Calvin
Stout, Jessica
Koetzner, Cheri A.
Payne, Anne F.
Bialosuknia, Sean M.
Banker, Elyse M.
Nolen, Taylor A.
Cameron, Craig E.
Ciota, Alexander T.
Maintenance of a host-specific minority mutation in the West Nile virus NS3
title Maintenance of a host-specific minority mutation in the West Nile virus NS3
title_full Maintenance of a host-specific minority mutation in the West Nile virus NS3
title_fullStr Maintenance of a host-specific minority mutation in the West Nile virus NS3
title_full_unstemmed Maintenance of a host-specific minority mutation in the West Nile virus NS3
title_short Maintenance of a host-specific minority mutation in the West Nile virus NS3
title_sort maintenance of a host-specific minority mutation in the west nile virus ns3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10428113/
https://www.ncbi.nlm.nih.gov/pubmed/37593454
http://dx.doi.org/10.1016/j.isci.2023.107468
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