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Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants

Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level beca...

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Autores principales: Koel, B F, Vigeveno, R M, Pater, M, Koekkoek, S M, Han, A X, Tuan, H M, Anh, T T N, Hung, N T, Thinh, L Q, Hai, L T, Ngoc, H T B, Chau, N V V, Ngoc, N M, Chokephaibulkit, K, Puthavathana, P, Kinh, N V, Trinh, T, Lee, R T C, Maurer-Stroh, S, Eggink, D, Thanh, T T, Tan, L V, van Doorn, H R, de Jong, M D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733607/
https://www.ncbi.nlm.nih.gov/pubmed/33343927
http://dx.doi.org/10.1093/ve/veaa088
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author Koel, B F
Vigeveno, R M
Pater, M
Koekkoek, S M
Han, A X
Tuan, H M
Anh, T T N
Hung, N T
Thinh, L Q
Hai, L T
Ngoc, H T B
Chau, N V V
Ngoc, N M
Chokephaibulkit, K
Puthavathana, P
Kinh, N V
Trinh, T
Lee, R T C
Maurer-Stroh, S
Eggink, D
Thanh, T T
Tan, L V
van Doorn, H R
de Jong, M D
author_facet Koel, B F
Vigeveno, R M
Pater, M
Koekkoek, S M
Han, A X
Tuan, H M
Anh, T T N
Hung, N T
Thinh, L Q
Hai, L T
Ngoc, H T B
Chau, N V V
Ngoc, N M
Chokephaibulkit, K
Puthavathana, P
Kinh, N V
Trinh, T
Lee, R T C
Maurer-Stroh, S
Eggink, D
Thanh, T T
Tan, L V
van Doorn, H R
de Jong, M D
author_sort Koel, B F
collection PubMed
description Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir-resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir-resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir-resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4–7 days post-treatment delay in emergence of oseltamivir-resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants.
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spelling pubmed-77336072020-12-17 Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants Koel, B F Vigeveno, R M Pater, M Koekkoek, S M Han, A X Tuan, H M Anh, T T N Hung, N T Thinh, L Q Hai, L T Ngoc, H T B Chau, N V V Ngoc, N M Chokephaibulkit, K Puthavathana, P Kinh, N V Trinh, T Lee, R T C Maurer-Stroh, S Eggink, D Thanh, T T Tan, L V van Doorn, H R de Jong, M D Virus Evol Research Article Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir-resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir-resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir-resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4–7 days post-treatment delay in emergence of oseltamivir-resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants. Oxford University Press 2020-12-01 /pmc/articles/PMC7733607/ /pubmed/33343927 http://dx.doi.org/10.1093/ve/veaa088 Text en © The Author(s) 2020. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Koel, B F
Vigeveno, R M
Pater, M
Koekkoek, S M
Han, A X
Tuan, H M
Anh, T T N
Hung, N T
Thinh, L Q
Hai, L T
Ngoc, H T B
Chau, N V V
Ngoc, N M
Chokephaibulkit, K
Puthavathana, P
Kinh, N V
Trinh, T
Lee, R T C
Maurer-Stroh, S
Eggink, D
Thanh, T T
Tan, L V
van Doorn, H R
de Jong, M D
Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants
title Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants
title_full Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants
title_fullStr Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants
title_full_unstemmed Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants
title_short Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants
title_sort longitudinal sampling is required to maximize detection of intrahost a/h3n2 virus variants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733607/
https://www.ncbi.nlm.nih.gov/pubmed/33343927
http://dx.doi.org/10.1093/ve/veaa088
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