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Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission

Dengue virus (DENV) infection of an individual human or mosquito host produces a dynamic population of closely-related sequences. This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species, but it remains poorly c...

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Autores principales: Sim, Shuzhen, Aw, Pauline P. K., Wilm, Andreas, Teoh, Garrett, Hue, Kien Duong Thi, Nguyen, Nguyet Minh, Nagarajan, Niranjan, Simmons, Cameron P., Hibberd, Martin L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556672/
https://www.ncbi.nlm.nih.gov/pubmed/26325059
http://dx.doi.org/10.1371/journal.pntd.0004052
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author Sim, Shuzhen
Aw, Pauline P. K.
Wilm, Andreas
Teoh, Garrett
Hue, Kien Duong Thi
Nguyen, Nguyet Minh
Nagarajan, Niranjan
Simmons, Cameron P.
Hibberd, Martin L.
author_facet Sim, Shuzhen
Aw, Pauline P. K.
Wilm, Andreas
Teoh, Garrett
Hue, Kien Duong Thi
Nguyen, Nguyet Minh
Nagarajan, Niranjan
Simmons, Cameron P.
Hibberd, Martin L.
author_sort Sim, Shuzhen
collection PubMed
description Dengue virus (DENV) infection of an individual human or mosquito host produces a dynamic population of closely-related sequences. This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species, but it remains poorly characterized. To track changes in viral intra-host genetic diversity during horizontal transmission, we infected Aedes aegypti mosquitoes by allowing them to feed on DENV2-infected patients. We then performed whole-genome deep-sequencing of human- and matched mosquito-derived DENV samples on the Illumina platform and used a sensitive variant-caller to detect single nucleotide variants (SNVs) within each sample. >90% of SNVs were lost upon transition from human to mosquito, as well as from mosquito abdomen to salivary glands. Levels of viral diversity were maintained, however, by the regeneration of new SNVs at each stage of transmission. We further show that SNVs maintained across transmission stages were transmitted as a unit of two at maximum, suggesting the presence of numerous variant genomes carrying only one or two SNVs each. We also present evidence for differences in selection pressures between human and mosquito hosts, particularly on the structural and NS1 genes. This analysis provides insights into how population drops during transmission shape RNA virus genetic diversity, has direct implications for virus evolution, and illustrates the value of high-coverage, whole-genome next-generation sequencing for understanding viral intra-host genetic diversity.
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spelling pubmed-45566722015-09-10 Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission Sim, Shuzhen Aw, Pauline P. K. Wilm, Andreas Teoh, Garrett Hue, Kien Duong Thi Nguyen, Nguyet Minh Nagarajan, Niranjan Simmons, Cameron P. Hibberd, Martin L. PLoS Negl Trop Dis Research Article Dengue virus (DENV) infection of an individual human or mosquito host produces a dynamic population of closely-related sequences. This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species, but it remains poorly characterized. To track changes in viral intra-host genetic diversity during horizontal transmission, we infected Aedes aegypti mosquitoes by allowing them to feed on DENV2-infected patients. We then performed whole-genome deep-sequencing of human- and matched mosquito-derived DENV samples on the Illumina platform and used a sensitive variant-caller to detect single nucleotide variants (SNVs) within each sample. >90% of SNVs were lost upon transition from human to mosquito, as well as from mosquito abdomen to salivary glands. Levels of viral diversity were maintained, however, by the regeneration of new SNVs at each stage of transmission. We further show that SNVs maintained across transmission stages were transmitted as a unit of two at maximum, suggesting the presence of numerous variant genomes carrying only one or two SNVs each. We also present evidence for differences in selection pressures between human and mosquito hosts, particularly on the structural and NS1 genes. This analysis provides insights into how population drops during transmission shape RNA virus genetic diversity, has direct implications for virus evolution, and illustrates the value of high-coverage, whole-genome next-generation sequencing for understanding viral intra-host genetic diversity. Public Library of Science 2015-09-01 /pmc/articles/PMC4556672/ /pubmed/26325059 http://dx.doi.org/10.1371/journal.pntd.0004052 Text en © 2015 Sim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sim, Shuzhen
Aw, Pauline P. K.
Wilm, Andreas
Teoh, Garrett
Hue, Kien Duong Thi
Nguyen, Nguyet Minh
Nagarajan, Niranjan
Simmons, Cameron P.
Hibberd, Martin L.
Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission
title Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission
title_full Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission
title_fullStr Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission
title_full_unstemmed Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission
title_short Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission
title_sort tracking dengue virus intra-host genetic diversity during human-to-mosquito transmission
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556672/
https://www.ncbi.nlm.nih.gov/pubmed/26325059
http://dx.doi.org/10.1371/journal.pntd.0004052
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