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EVOLUTION OF FELINE AND CANINE PARVOVIRUSES: UNDERSTANDING THE CAPSID STRUCTURE, THE NATURAL VARIATION, AND THE ANTIBODY SELECTION

dc.contributor.authorLopez-Astacio, Robert
dc.contributor.chairParrish, Colinen_US
dc.contributor.committeeMemberAguilar-Carreno, Hectoren_US
dc.contributor.committeeMemberParker, Johnen_US
dc.contributor.committeeMemberWhittaker, Garyen_US
dc.date.accessioned2024-01-31T21:19:25Z
dc.date.available2024-01-31T21:19:25Z
dc.date.issued2023-05
dc.description.abstractParvoviruses, including feline (FPV) and canine parvovirus (CPV), are the smallest and structurally simplest viruses ever described, both in their genome composition as well as their overall icosahedral structure. Their capsids are composed of variants of a single structural protein that controls many of the required steps for replication and the interaction with many host- derived ligands and molecules, including cellular receptors and antibodies. Despite their apparent simplicity, FPV and CPV present complex and dynamic interactions that lead to wide host ranges, rapid adaptation, successful sustained transmission, host immunity evasion, and a long evolutionary trajectory. This dissertation used FPV and CPV as models to better understand capsid structures and functions, to describe the genetic variation in virus populations as a result of their many and intricate interactions with a myriad of host-derived molecules such as receptors and antibodies, and to describe and characterize their overall evolutionary history.I found that CPV capsids mutate in the face of neutralizing antibodies. Those mutated residues are within or close to antibody footprints and avoid receptor binding sites despite the overlapping of those two. Antibody-selected mutations in capsids result in decreased binding to the antibodies, showing that those are escape mutations. Additionally, I found that those antibody escape mutations are restricted to a reduced number of residues in the viral capsid when using mutated versions of the antibodies. A great number of these mutations are also found in natural isolates and those might be linked to the variants that evade the host-immune system. Despite the long evolutionary trajectory of FPV, I found that all FPV variants are ~99% identical in nucleotide sequence. I was also able to reveal the landscape of mutations that have become widespread in the FPV genomes during 57 years of its evolutionary history in cats and other susceptible hosts, and I compared that to what has been seen for CPV. I also found that ~66% of the substitutions that became widespread in CPV genomes are present at low frequencies in FPV variants and that most of the FPV vaccines currently in use are derived from one of the first isolated 1960s virus. The FPV-like viruses have evolved at similar rates to CPV- derived viruses in different hosts, but most substitutions in the capsid protein gene were silent changes. The small number of coding changes in the FPV lineage do not alter the known antigenic epitopes of parvoviruses, suggesting the continued efficaciousness of the 60-year-old vaccines in cats. The results of this dissertation provide new information that is immediately relevant to the emergence of new viruses and also provides new insights into how viruses evolve, adapt, overcome species barriers, and persist in natural reservoirs, as well as revealing the complicated and sophisticated roles of parvovirus capsids despite their seeming simplicity.en_US
dc.identifier.doihttps://doi.org/10.7298/p8gb-sg18
dc.identifier.otherLopezAstacio_cornellgrad_0058F_13548
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:13548
dc.identifier.urihttps://hdl.handle.net/1813/114090
dc.language.isoen
dc.subjectantibodiesen_US
dc.subjectcapsiden_US
dc.subjectevolutionen_US
dc.subjectmutationsen_US
dc.subjectparvovirusesen_US
dc.subjectstructureen_US
dc.titleEVOLUTION OF FELINE AND CANINE PARVOVIRUSES: UNDERSTANDING THE CAPSID STRUCTURE, THE NATURAL VARIATION, AND THE ANTIBODY SELECTIONen_US
dc.typedissertation or thesisen_US
dcterms.licensehttps://hdl.handle.net/1813/59810.2
thesis.degree.disciplineBiomedical and Biological Sciences
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Biomedical and Biological Sciences

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