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A paucigranulocytic asthma host environment promotes the emergence of virulent influenza viral variants.

ABSTRACT: Influenza virus has a high mutation rate, such that within one host different viral variants can emerge. Evidence suggests that influenza virus variants are more prevalent in pregnant and/or obese individuals due to their impaired interferon response. We have recently shown that the non-allergic, paucigranulocytic subtype of asthma is associated with impaired type I interferon production. Here, we seek to address if this is associated with an increased emergence of influenza virus variants. Compared to controls, mice with paucigranulocytic asthma had increased disease severity and an increased emergence of influenza virus variants. Specifically, PB1 mutations exclusively detected in asthmatic mice were associated with increased polymerase activity. Furthermore, asthmatic host-derived virus led to increased disease severity in wild-type mice. Taken together, these data suggest that at least a subset of patients with asthma may be more susceptible to severe influenza and may be a possible source of new influenza virus variants.

SUBMITTER: Hulme KD

PROVIDER: S-EPMC7886327 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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A paucigranulocytic asthma host environment promotes the emergence of virulent influenza viral variants.

Hulme Katina D KD Karawita Anjana C AC Pegg Cassandra C Bunte Myrna Jm MJ Bielefeldt-Ohmann Helle H Bloxham Conor J CJ Van den Hoecke Silvie S Setoh Yin Xiang YX Vrancken Bram B Spronken Monique M Steele Lauren E LE Verzele Nathalie Aj NA Upton Kyle R KR Khromykh Alexander A AA Chew Keng Yih KY Sukkar Maria M Phipps Simon S Short Kirsty R KR

eLife 20210216

Influenza virus has a high mutation rate, such that within one host different viral variants can emerge. Evidence suggests that influenza virus variants are more prevalent in pregnant and/or obese individuals due to their impaired interferon response. We have recently shown that the non-allergic, paucigranulocytic subtype of asthma is associated with impaired type I interferon production. Here, we seek to address if this is associated with an increased emergence of influenza virus variants. Comp ...[more]

PMID: 33588989

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Project description:The successive emergence of SARS-CoV-2 mutations has led to an unprecedented increase in COVID-19 incidence worldwide. Currently, vaccination is considered to be the best available solution to control the ongoing COVID-19 pandemic. However, public opposition to vaccination persists in many countries, which can lead to increased COVID-19 caseloads and hence greater opportunities for vaccine-evasive mutant strains to arise. To determine the extent that public opinion regarding vaccination can induce or hamper the emergence of new variants, we develop a model that couples a compartmental disease transmission framework featuring two strains of SARS-CoV-2 with game theoretical dynamics on whether or not to vaccinate. We combine semi-stochastic and deterministic simulations to explore the effect of mutation probability, perceived cost of receiving vaccines, and perceived risks of infection on the emergence and spread of mutant SARS-CoV-2 strains. We find that decreasing the perceived costs of being vaccinated and increasing the perceived risks of infection (that is, decreasing vaccine hesitation) will decrease the possibility of vaccine-resistant mutant strains becoming established by about fourfold for intermediate mutation rates. Conversely, we find increasing vaccine hesitation to cause both higher probability of mutant strains emerging and more wild-type cases after the mutant strain has appeared. We also find that once a new variant has emerged, perceived risk of being infected by the original variant plays a much larger role than perceptions of the new variant in determining future outbreak characteristics. Furthermore, we find that rapid vaccination under non-pharmaceutical interventions is a highly effective strategy for preventing new variant emergence, due to interaction effects between non-pharmaceutical interventions and public support for vaccination. Our findings indicate that policies that combine combating vaccine-related misinformation with non-pharmaceutical interventions (such as reducing social contact) will be the most effective for avoiding the establishment of harmful new variants.

Dataset Information

A paucigranulocytic asthma host environment promotes the emergence of virulent influenza viral variants.

Publications

A paucigranulocytic asthma host environment promotes the emergence of virulent influenza viral variants.

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