Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children
- Amsterdam University Medical Center, Netherlands
- National Institute of Hygiene and Epidemiology, Viet Nam
- National Institute Of Hygiene And Epidemiology, Viet Nam
- Ha Nam Centre for Disease Control, Viet Nam
- Children's Hospital 2, Viet Nam
- Children's Hospital 1, Viet Nam
- Vietnam National Children's Hospital, Viet Nam
- Mahidol University, Thailand
- Hospital for Tropical Diseases, Viet Nam
- National Hospital for Tropical Diseases, Viet Nam
- Radboud University, Netherlands
- University of Oxford, United Kingdom
- University of Melbourne, Australia
Abstract
The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on infections in healthy adults based on single timepoint data. Here, we analysed the within-host evolution of 82 longitudinally-sampled individuals, mostly young children, infected with A/H1N1pdm09 or A/H3N2 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous minority variants were more prevalent than synonymous ones. For A/H3N2 viruses in young children, early infection was dominated by purifying selection. As these infections progressed, nonsynonymous variants typically increased in frequency even when within-host virus titres decreased. Unlike the short-lived infections of adults where de novo within-host variants are rare, longer infections in young children allow for the maintenance of virus diversity via mutation-selection balance creating potentially important opportunities for within-host virus evolution.
Data availability
All raw sequence data have been deposited at NCBI sequence read archive under BioProject Accession number PRJNA722099. All custom Python code and Jupyter notebooks to reproduce the analyses in this paper are available online: https://github.com/AMC-LAEB/Within_Host_H3vH1.
Article and author information
Author details
Zandra C Felix Garza
Matthijs RA Welkers
Funding
H2020 European Research Council (818353)
- Alvin X Han
- Zandra C Felix Garza
- Colin A Russell
National Institute of Allergy and Infectious Diseases (N01-A0-50042)
- Matthijs RA Welkers
- René M Vigeveno
- Nhu Duong Tran
- Thi Quynh Mai Le
- Thai Pham Quang
- Dinh Thoang Dang
- Thi Ngoc Anh Tran
- Manh Tuan Ha
- Thanh Hung Nguyen
- Quoc Thinh Le
- Thanh Hai Le
- Thi Bich Ngoc Hoang
- Kulkanya Chokephaibulkit
- Pilaipan Puthavathana
- Van Vinh Chau Nguyen
- My Ngoc Nghiem
- Van Kinh Nguyen
- Tuyet Trinh Dao
- Tinh Hien Tran
- Heiman FL Wertheim
- Peter W Horby
- Annette Fox
- H Rogier van Doorn
- Dirk Eggink
- Menno D de Jong
National Institutes of Health (HHSN272200500042C)
- Matthijs RA Welkers
- René M Vigeveno
- Nhu Duong Tran
- Thi Quynh Mai Le
- Thai Pham Quang
- Dinh Thoang Dang
- Thi Ngoc Anh Tran
- Manh Tuan Ha
- Thanh Hung Nguyen
- Quoc Thinh Le
- Thanh Hai Le
- Thi Bich Ngoc Hoang
- Kulkanya Chokephaibulkit
- Pilaipan Puthavathana
- Van Vinh Chau Nguyen
- My Ngoc Nghiem
- Van Kinh Nguyen
- Tuyet Trinh Dao
- Tinh Hien Tran
- Heiman FL Wertheim
- Peter W Horby
- Annette Fox
- H Rogier van Doorn
- Dirk Eggink
- Menno D de Jong
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The Institutional Review Board of all hospitals, the National Institute of Allergy and Infectious Diseases, and the Oxford Tropical Research Ethics Committee approved the study. Written informed consent was given by all patients (or proxies).
Copyright
© 2021, Han et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,856
- views
-
- 218
- downloads
-
- 13
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children
eLife 10:e68917.
https://doi.org/10.7554/eLife.68917
Further reading
-
- Computational and Systems Biology
- Evolutionary Biology
As pathogens spread in a population of hosts, immunity is built up, and the pool of susceptible individuals are depleted. This generates selective pressure, to which many human RNA viruses, such as influenza virus or SARS-CoV-2, respond with rapid antigenic evolution and frequent emergence of immune evasive variants. However, the host’s immune systems adapt, and older immune responses wane, such that escape variants only enjoy a growth advantage for a limited time. If variant growth dynamics and reshaping of host-immunity operate on comparable time scales, viral adaptation is determined by eco-evolutionary interactions that are not captured by models of rapid evolution in a fixed environment. Here, we use a Susceptible/Infected model to describe the interaction between an evolving viral population in a dynamic but immunologically diverse host population. We show that depending on strain cross-immunity, heterogeneity of the host population, and durability of immune responses, escape variants initially grow exponentially, but lose their growth advantage before reaching high frequencies. Their subsequent dynamics follows an anomalous random walk determined by future escape variants and results in variant trajectories that are unpredictable. This model can explain the apparent contradiction between the clearly adaptive nature of antigenic evolution and the quasi-neutral dynamics of high-frequency variants observed for influenza viruses.
-
- Ecology
- Evolutionary Biology
Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs of the family Dendrobatidae have evolved the novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling for alkaloids has been biased towards colorful species, without similar attention paid to inconspicuous ones that are often assumed to be undefended. As a result, our understanding of how chemical defense evolved in this group is incomplete. Here, we provide new data showing that, in contrast to previous studies, species from each undefended poison frog clade have measurable yet low amounts of alkaloids. We confirm that undefended dendrobatids regularly consume mites and ants, which are known sources of alkaloids. Thus, our data suggest that diet is insufficient to explain the defended phenotype. Our data support the existence of a phenotypic intermediate between toxin consumption and sequestration — passive accumulation — that differs from sequestration in that it involves no derived forms of transport and storage mechanisms yet results in low levels of toxin accumulation. We discuss the concept of passive accumulation and its potential role in the origin of chemical defenses in poison frogs and other toxin-sequestering organisms. In light of ideas from pharmacokinetics, we incorporate new and old data from poison frogs into an evolutionary model that could help explain the origins of acquired chemical defenses in animals and provide insight into the molecular processes that govern the fate of ingested toxins.
