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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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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. |
format | Online Article Text |
id | pubmed-10428113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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