Molecular signals of arms race evolution between RNA viruses and their hosts

Lytras, Spyridon (2023) Molecular signals of arms race evolution between RNA viruses and their hosts. PhD thesis, University of Glasgow.

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Viruses are intracellular parasites that hijack their hosts’ cellular machinery to replicate themselves. This creates an evolutionary “arms race” between hosts and viruses, where the former develop mechanisms to restrict viral infection and the latter evolve ways to circumvent these molecular barriers. In this thesis, I explore examples of this virus-host molecular interplay, focusing on events in the evolutionary histories of both viruses and hosts. The thesis begins by examining how recombination, the exchange of genetic material between related viruses, expands the genomic diversity of the Sarbecovirus subgenus, which includes SARS-CoV responsible for the 2002 SARS epidemic and SARS-CoV-2 responsible for the COVID-19 pandemic. On the host side, I examine the evolutionary interaction between RNA viruses and two interferon-stimulated genes expressed in hosts. First, I show how the 2′-5′-oligoadenylate synthetase 1 (OAS1) gene of horseshoe bats (Rhinolophoidea), the reservoir host of sarbecoviruses, lost its anti-coronaviral activity at the base of this bat superfamily. By reconstructing the Rhinolophoidea common ancestor OAS1 protein, I first validate the loss of antiviral function and highlight the implications of this event in the virus-host association between sarbecoviruses and horseshoe bat hosts. Second, I focus on the evolution of the human butyrophilin subfamily 3 member A3 (BTN3A3) gene which restricts infection by avian influenza A viruses (IAV). The evolutionary analysis reveals that BTN3A3’s anti-IAV function was gained within the primates and that specific amino acid substitutions need to be acquired in IAVs’ NP protein to evade the human BTN3A3 activity. Gain of BTN3A3-evasion-conferring substitutions correlate with all major human IAV pandemics and epidemics, making these NP residues key markers for IAV transmissibility potential to humans. In the final part of the thesis, I present a novel approach for evaluating dinucleotide compositional biases in virus genomes. An application of my metric on the Flaviviridae virus family uncovers how ancestral host shifts of these viruses correlate with adaptive shifts in their genomes’ dinucleotide representation. Collectively, the contents of this thesis extend our understanding of how viruses interact with their hosts along their intertangled evolution and provide insights into virus host switching and pandemic preparedness.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology
Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Supervisor's Name: Hughes, Dr. Joseph, Wilson, Professor Sam and Robertson, Professor David
Date of Award: 2023
Depositing User: Theses Team
Unique ID: glathesis:2023-83882
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 26 Oct 2023 10:47
Last Modified: 26 Oct 2023 11:44
Thesis DOI: 10.5525/gla.thesis.83882
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