Influenza A genomic diversity during human infections underscores the strength of genetic drift and the existence of tight transmission bottlenecks

Virus Evolution, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 1, 2024

Abstract Influenza infections result in considerable public health and economic impacts each year. One of the contributing factors to high annual incidence human influenza is virus’s ability evade acquired immunity through continual antigenic evolution. Understanding evolutionary forces that act within between hosts therefore critical interpreting past trends virus evolution predicting future ones. Several studies have analyzed longitudinal patterns A genetic diversity natural assess relative contributions selection drift on within-host However, these infections, viral populations harbor very few single-nucleotide variants, limiting our resolution understanding acting vivo. Furthermore, low levels limit infer extent across transmission events. Here, we propose use genomic as an alternative signal better understand within- between-host Specifically, focus dynamics defective genomes (DVGs), which large internal deletions one or more eight gene segments. Our analyses DVGs show are highly dynamic hosts, corroborating previous findings based point toward importance driving analysis DVG pairs indicates rarely appeared be shared, indicating presence tight bottlenecks. demonstrate can used complement reveal processes drive hosts.

Language: Английский

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Barcoded SARS-CoV-2 viruses define the impact of duration and route of exposure on the transmission bottleneck in a hamster model

Science Advances, Journal Year: 2025, Volume and Issue: 11(3)

Published: Jan. 15, 2025

The transmission bottleneck, defined as the number of viruses shed from one host to infect another, is an important determinant rate virus evolution and level immunity required protect against transmission. Despite its importance, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) bottleneck remains poorly characterized. We adapted a SARS-CoV-2 reverse genetics system generate pool >200 isogenic harboring specific 6-nucleotide barcodes, infected donor hamsters with this pool, exposed contact paired donors, varying duration route exposure. Following exposure, nasal turbinates, trachea, lungs were collected barcodes in each tissue was enumerated. found that longer more direct exposures increased upper airway primary source transmitted model. Together, these findings highlight utility barcoded tools rigorously study

Language: Английский

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Dispersal of influenza virus populations within the respiratory tract shapes their evolutionary potential

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(4)

Published: Jan. 21, 2025

Viral infections are characterized by dispersal from an initial site to secondary locations within the host. How resultant spatial heterogeneity shapes within-host genetic diversity and viral evolutionary pathways is poorly understood. Here, we show that virus between nasal cavity trachea maintains therefore conducive adaptive evolution, whereas lungs gives rise population heterogeneity. We infected ferrets either intranasally or aerosol with a barcoded influenza A/California/07/2009 (H1N1) virus. At 1, 2, 4 days postinfection, was assessed collecting 52 samples throughout respiratory tract of each animal. Irrespective inoculation route, barcode compositions across turbinates were similar highly diverse, revealing little constraint on establishment infection in descent through trachea. Conversely, produced genetically distinct populations. Lung populations pauci-clonal, suggesting seeded location received relatively few genotypes. While gave at every lung sampled, after intranasal larger patches, indicative local expansion following seeding lungs. Throughout tract, declined over time, but new generated mutation. De novo variants often unique given location, indicating localized replication resulted divergence. In summary, operates differently regions contributes potential for evolution proceed independently multiple subpopulations.

Language: Английский

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Determinants of SARS-CoV-2 within-host evolutionary rates in persistently infected individuals

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

Abstract Understanding the within-host evolutionary dynamics of SARS-CoV-2, particularly in relation to variant emergence, is crucial for public health. From a community surveillance study, we identified 576 persistent infections, more common among males and those over 60. Our findings show significant variation rates individuals, driven by nonsynonymous mutations. Longer-lasting infections accumulated mutations faster, with no link demographics, vaccination status, virus lineage, or prior infection. The rate was high within N-terminal receptor binding domains Spike. ORF6 under strong purifying selection, making it potential therapeutic target. We also 379 recurring mutations, half having negative fitness effect very low prevalence at between-host level, indicating some are favoured during infection but disadvantageous transmission. study highlights highly heterogenous nature evolution SARS-CoV-2 which may turn help inform future intervention strategies. Figure

Language: Английский

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Dispersal of influenza virus populations within the respiratory tract shapes their evolutionary potential

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 31, 2024

Abstract Viral infections are characterized by dispersal from an initial site to secondary locations within the host. How resultant spatial heterogeneity shapes within-host genetic diversity and viral evolutionary pathways is poorly understood. Here we show that between nasal cavity trachea maintains therefore conducive adaptive evolution, whereas lungs stochastic gives rise population heterogeneity. We infected ferrets either intranasally or aerosol with a barcoded influenza A/California/07/2009 (H1N1) virus. At 1, 2 4 days post infection, was assessed collecting 52 samples throughout respiratory tract of each animal. Irrespective inoculation route, barcode compositions across turbinates were similar highly diverse, revealing little constraint on establishment infection in descent through trachea. By comparison, produced genetically distinct populations. Lung populations pauci-clonal, suggesting seeded location received relatively few genotypes. While gave at every lung sampled, after intranasal larger patches, indicative local expansion following seeding lungs. Throughout tract, declined over time, but new generated mutation. De novo variants often unique given location, indicating localized replication resulted divergence. In summary, operates differently regions contributes potential for evolution proceed independently multiple subpopulations.

Language: Английский

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Barcoded SARS-CoV-2 viruses define the impact of time and route of transmission on the transmission bottleneck in a Syrian hamster model

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

The transmission bottleneck, defined as the number of viruses that transmit from one host to infect another, is an important determinant rate virus evolution and level immunity required protect against transmission. Despite its importance, SARS-CoV-2's bottleneck remains poorly characterized, in part due a lack quantitative measurement tools. To address this, we adapted SARS-CoV-2 reverse genetics system generate pool >200 isogenic harboring specific 6-nucleotide barcodes inserted ORF10, non-translated ORF. We directly inoculated donor Syrian hamsters intranasally with this barcoded exposed paired naïve contact hamster each donor. Following exposure, nasal turbinates, trachea, lungs were collected, viral titers measured, tissue enumerated quantify bottleneck. duration route (airborne, direct contact, fomite) exposure varied assess their impact on In airborne-exposed hamsters, increased longer durations. found produced largest (average 27 BCs), followed by airborne 16 BCs) then fomite 8 BCs). Interestingly, detected unique BCs both upper lower respiratory tract animals all routes suggesting can lungs. Altogether, these findings highlight utility tools rigorously study future, will strengthen studies immune factors influence

Language: Английский

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Intra-host variability of SARS-CoV-2: Patterns, causes and impact on COVID-19

Virology, Journal Year: 2024, Volume and Issue: 603, P. 110366 - 110366

Published: Dec. 22, 2024

Language: Английский

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