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Title: Molecular determinants of influenza A virus cross-species jumps
Author: Coburn, Alice Miranda
ISNI:       0000 0004 6422 7140
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2017
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Influenza A viruses (IAVs) represent a significant risk to human and animal health and thus determining the mechanisms of cross-species transmission is critical in understanding viral emergence. H3N8 equine influenza virus (EIV) is a virus of avian origin that emerged in horses in the early 1960s and is still circulating in horses despite the availability of vaccines. Therefore, H3N8 EIV provides unique opportunities to study the underpinning mechanisms of cross-species jumps and adaptation in mammalian hosts. The aim of this project was to determine the role of evolution on EIV adaptation to the horse. To this end, equine and avian cell lines were infected as well as horse tracheal explants with a panel of phylogenetically distinct EIVs and compared their infection phenotypes. Viral replication was quantified and changes in the histology and ciliary activity of infected explants were assessed to compare the phenotype of infection of each virus. Phylogenetically distinct EIVs exhibited different infection phenotypes: while early EIVs grew more efficiently in avian cells, late EIVs grew to higher titres in equine explants. This phenotype was demonstrated to be largely due to the late EIV viral polymerase. Using an in vitro measure of polymerase activity, late EIVs were observed to have more efficient activity in mammalian cells than early EIVs. The Polymerase Acidic (PA) and Nucleoprotein (NP) segments were shown to be the greatest drivers of the mammalian-adapted polymerase phenotype. Including either of these segments from a late EIV in the polymerase complex significantly increased minireplicon activity. Our results suggest that EIV adapted to the horse along its evolutionary history partly by mutations in the PA and NP genes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR355 Virology