ORCID Profile
0000-0002-1912-4500
Current Organisation
University of Nottingham
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Publisher: American Society for Microbiology
Date: 15-07-2010
DOI: 10.1128/JVI.00112-10
Abstract: Determining the evolutionary basis of cross-species transmission and immune evasion is key to understanding the mechanisms that control the emergence of either new viruses or novel antigenic variants with pandemic potential. The hemagglutinin glycoprotein of influenza A viruses is a critical host range determinant and a major target of neutralizing antibodies. Equine influenza virus (EIV) is a significant pathogen of the horse that causes periodical outbreaks of disease even in populations with high vaccination coverage. EIV has also jumped the species barrier and emerged as a novel respiratory pathogen in dogs, canine influenza virus. We studied the dynamics of equine influenza virus evolution in horses at the intrahost level and how this evolutionary process is affected by interhost transmission in a natural setting. To this end, we performed clonal sequencing of the hemagglutinin 1 gene derived from in idual animals at different times postinfection. Our results show that despite the population consensus sequence remaining invariant, genetically distinct subpopulations persist during the course of infection and are also transmitted, with some variants likely to change antigenicity. We also detected a natural case of mixed infection in an animal infected during an outbreak of equine influenza, raising the possibility of reassortment between different strains of virus. In sum, our data suggest that transmission bottlenecks may not be as narrow as originally perceived and that the genetic ersity required to adapt to new host species may be partially present in the donor host and potentially transmitted to the recipient host.
Publisher: Microbiology Society
Date: 08-2015
DOI: 10.1099/JGV.0.000241
Publisher: The Royal Society
Date: 07-08-2004
Publisher: Oxford University Press (OUP)
Date: 19-07-2006
DOI: 10.1093/JAC/DKL321
Abstract: Viruses resistant to zanamivir have been generated in vitro, but no resistant virus has yet been isolated from a zanamivir-treated immunocompetent patient. In contrast most resistant viruses isolated from oseltamivir-treated patients correspond to those selected in vitro. However, despite mutations being in conserved residues in the neuraminidase (NA) they do not confer resistance in all NA subtypes. We have used reverse genetics and the recombinant baculovirus expression system for investigating reasons for the lack of isolation of zanamivir-resistant H3N2 viruses and for further exploring subtype-specific oseltamivir resistance. H3N2 viruses generated by reverse genetics with H274Y, R292K E119V and E119D mutations were rescued. Those with E119G, E119A or R152K mutations could only be rescued in the presence of exogenous NA and after passage in the absence of exogenous NA only isolates that had reverted to the wild-type NA or, surprisingly, E119G/A to E119V NA were isolated. Mutations conferring zanamivir resistance significantly affected enzyme activity, virus replication or NA thermal stability. E119V viruses were stable and grew to similar titres as wild-type virus, consistent with their isolation from oseltamivir-treated patients. Mutations conferring oseltamivir resistance in N1 (H274Y) and B (R152K) NAs also conferred resistance in recombinant G70C N9 NA expressed in insect cells. These data suggest that zanamivir-resistant H3N2 viruses may not readily arise in vivo due to their poor viability. The G70C N9 NA may also provide a useful model for understanding the structural basis of subtype-specific drug resistance.
Publisher: American Society for Microbiology
Date: 15-04-2013
DOI: 10.1128/JVI.03379-12
Abstract: Influenza A viruses are characterized by their ability to evade host immunity, even in vaccinated in iduals. To determine how prior immunity shapes viral ersity in vivo , we studied the intra- and interhost evolution of equine influenza virus in vaccinated horses. Although the level and structure of genetic ersity were similar to those in naïve horses, intrahost bottlenecks may be more stringent in vaccinated animals, and mutations shared among horses often fall close to putative antigenic sites.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-01-2004
Abstract: A key priority for infectious disease research is to clarify how pathogen genetic variation, modulated by host immunity, transmission bottlenecks, and epidemic dynamics, determines the wide variety of pathogen phylogenies observed at scales that range from in idual host to population. We call the melding of immunodynamics, epidemiology, and evolutionary biology required to achieve this synthesis pathogen “phylodynamics.” We introduce a phylodynamic framework for the dissection of dynamic forces that determine the ersity of epidemiological and phylogenetic patterns observed in RNA viruses of vertebrates. A central pillar of this model is the Evolutionary Infectivity Profile, which captures the relationship between immune selection and pathogen transmission.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Janet Daly.