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

Katina D Hulme; Anjana C Karawita; Cassandra Pegg; Myrna Jm Bunte; Helle Bielefeldt-Ohmann; Conor J Bloxham; Silvie Van den Hoecke; Yin Xiang Setoh; Bram Vrancken; Monique Spronken; Lauren E Steele; Nathalie Aj Verzele; Kyle R Upton; Alexander A Khromykh; Keng Yih Chew; Maria Sukkar; Simon Phipps; Kirsty R Short

doi:10.7554/eLife.61803

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

Elife. 2021 Feb 16:10:e61803. doi: 10.7554/eLife.61803.

Authors

Katina D Hulme¹, Anjana C Karawita¹, Cassandra Pegg¹, Myrna Jm Bunte¹, Helle Bielefeldt-Ohmann^{1

2

3}, Conor J Bloxham⁴, Silvie Van den Hoecke^{5

6}, Yin Xiang Setoh^{1

2

7}, Bram Vrancken⁸, Monique Spronken⁹, Lauren E Steele¹, Nathalie Aj Verzele¹, Kyle R Upton¹, Alexander A Khromykh^{1

2}, Keng Yih Chew¹, Maria Sukkar¹⁰, Simon Phipps^{2

11}, Kirsty R Short^{1

2}

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
² Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.
³ School of Veterinary Science, The University of Queensland, Brisbane, Australia.
⁴ School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
⁵ VIB-UGent Center for Medical Biotechnology, Ghent, Belgium.
⁶ Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
⁷ Environmental Health Institute, National Environment Agency, Singapore, Singapore.
⁸ KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory of Evolutionary and Computational Virology, Leuven, Belgium.
⁹ Department of Viroscience, Erasmus MC, Rotterdam, Netherlands.
¹⁰ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Australia; Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, NSW, Australia.
¹¹ QIMR Berghofer Medical Research Institute, Brisbane, Australia.

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.

Keywords: asthma; host-pathogen evolution; human; immunology; infectious disease; inflammation; influenza virus; interferons; microbiology; mouse; mutation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma / virology*
Female
Host-Pathogen Interactions
Influenza A Virus, H1N1 Subtype / pathogenicity*
Male
Mice
Mice, Inbred C57BL
Orthomyxoviridae Infections / virology*
Receptor for Advanced Glycation End Products / deficiency

Substances

Receptor for Advanced Glycation End Products

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.