Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage

Amat, J. A.R. et al. (2021) Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage. PLoS Pathogens, 17(12), e1010174. (doi: 10.1371/journal.ppat.1010174) (PMID:34919598) (PMCID:PMC8735595)

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Abstract

The mechanisms and consequences of genome evolution on viral fitness following host shifts are poorly understood. In addition, viral fitness -the ability of an organism to reproduce and survive- is multifactorial and thus difficult to quantify. Influenza A viruses (IAVs) circulate broadly among wild birds and have jumped into and become endemic in multiple mammalian hosts, including humans, pigs, dogs, seals, and horses. H3N8 equine influenza virus (EIV) is an endemic virus of horses that originated in birds and has been circulating uninterruptedly in equine populations since the early 1960s. Here, we used EIV to quantify changes in infection phenotype associated to viral fitness due to genome-wide changes acquired during long-term adaptation. We performed experimental infections of two mammalian cell lines and equine tracheal explants using the earliest H3N8 EIV isolated (A/equine/Uruguay/63 [EIV/63]), and A/equine/Ohio/2003 (EIV/2003), a monophyletic descendant of EIV/63 isolated 40 years after the emergence of H3N8 EIV. We show that EIV/2003 exhibits increased resistance to interferon, enhanced viral replication, and a more efficient cell-to-cell spread in cells and tissues. Transcriptomics analyses revealed virus-specific responses to each virus, mainly affecting host immunity and inflammation. Image analyses of infected equine respiratory explants showed that despite replicating at higher levels and spreading over larger areas of the respiratory epithelium, EIV/2003 induced milder lesions compared to EIV/63, suggesting that adaptation led to reduced tissue pathogenicity. Our results reveal previously unknown links between virus genotype and the host response to infection, providing new insights on the relationship between virus evolution and fitness.

Item Type:Articles
Additional Information:Funding: PRM was supported by the Medical Research Council of the United Kingdom (Grant MC_UU_12014/9), the Horserace Betting Levy Board (Grants 779 and 797), the Biotechnology and Biological Sciences Research Council (Grants BB/V002821/1 and BB/V004697/1). JARA was supported by the Horserace Betting Levy Board and the University of Glasgow School of Veterinary Medicine VetFund, the Georgina Gardner Endowment (grant number 145813-01) and the John Crawford endowment (grant number 123939-01). QG was supported by the Medical Research Council of the United Kingdom (grant MC_UU_12014/12).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marchesi, Dr Francesco and Gu, Dr Quan and Amat, Mr Julien and Crispell, JOANNA and Goldfarb, Daniel Max and Chauche, Dr Caroline and Coburn, Alice Miranda and Marshall, Dr John and Tong, Dr Lily and Mair, Mr Daniel and Murcia, Professor Pablo and Patton, Veronica and Gonzalez, Ms Gaelle
Authors: Amat, J. A.R., Patton, V., Chauche, C., Goldfarb, D. M., Crispell, J., Gu, Q., Coburn, A. M., Gonzalez, G., Mair, D., Tong, L., Martinez-Sobrido, L., Marshall, J. F., Marchesi, F., and Murcia, P. R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Published Online:17 December 2021
Copyright Holders:Copyright: © 2021 Amat et al
First Published:First published in PLoS Pathogens 17(12): e1010174
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630Quinquennial Core FundsMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/9III-MRC-GU CVR Support Services
Medical Research Council (MRC)MC_UU_12014/12
310129Genomic epidemiology of equine influenza virus in the United KingdomPablo MurciaBiotechnology and Biological Sciences Research Council (BBSRC)BB/V002821/1III - Centre for Virus Research
309834TBCPablo MurciaBiotechnology and Biological Sciences Research Council (BBSRC)BB/V004697/1Institute of Biodiversity, Animal Health and Comparative Medicine