Exploring evolutionary dynamics of influenza viruses through the lens of equine influenza

Bone, Jordan (2025) Exploring evolutionary dynamics of influenza viruses through the lens of equine influenza. PhD thesis, University of Glasgow.

Abstract

Though many vaccines exist to confer protection from Influenza A viruses, they remain viruses of great concern in both mammalian and avian species. Influenza A viruses circulate in many wild, domestic and human species; often with the potential to transmit between these populations. Emergence in these other populations can lead to widespread transmission and/or severe pathology and indeed has occurred multiple times over just the last century.
As obligate pathogens, influenza viruses are only able to evolve during infection of hosts, as it is the only setting in which they can replicate. However, in addition to the local environment (i.e. the infected host) influenza viruses must also adapt to transmission between hosts.
Differences between hosts can be minimal but may be as dramatic as alternative tissue tropism or even host species. This work aims to study how influenza viruses evolve both within infected hosts and across transmission events, and the interaction between these two,
sometimes competing, ecological niches that viruses must adapt to. Integral to the continued success of influenza viruses is the ability to circumvent the host immune system. Host adaptive immunity places strong selective pressures upon viral populations. Transmission experiments were carried out in which mixed populations of horses (either vaccinated or unvaccinated) were sequentially exposed to one another to create a five-step chain of transmission. The first experiment mixed naive individuals with horses that had received a multivalent vaccine, the second mixed naive horses with hosts that had received a univalent vaccine. Horses were nasally-swabbed daily in order to collect shed virus particles which could then be quantified and deep-sequenced.
137 qPCR values and 53 sequences of viral populations were collected. Differences in viral load, consensus genomes and lowfrequency mutations were observed across transmission chains and between vaccinated and unvaccinated hosts. Unvaccinated horses shed more virus than their vaccinated counterparts, though this difference was much greater when comparing naive hosts to those that received a multivalent vaccine. Conversely, genomic diversity at the consensus level appeared highest in hosts that received the monovalent vaccine - suggesting strong selective pressures that mutations are attempting to overcome. This genetic diversity however was not reflected in sub-consensus reads, where lessened selective pressures allowed for greater diversification of viruses replicating in unvaccinated hosts.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QL Zoology; Q Science > QR Microbiology > QR355 Virology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Supervisor's Name: Weir, Dr. William, Murcia, Professor Pablo R., Biek, Professor Roman and Orton, Dr. Richard
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85122
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 09 May 2025 15:38
• Last Modified: 09 May 2025 15:44
• Thesis DOI: 10.5525/gla.thesis.85122
• URI: https://theses.gla.ac.uk/id/eprint/85122