Extrinsic and intrinsic drivers of feline immunodeficiency virus evolution in the mountain lion
| dc.contributor.author | Malmberg, Jennifer L., author | |
| dc.contributor.author | VandeWoude, Sue, advisor | |
| dc.contributor.author | Crooks, Kevin, committee member | |
| dc.contributor.author | Quackenbush, Sandra, committee member | |
| dc.contributor.author | Perera, Rushika, committee member | |
| dc.date.accessioned | 2019-01-07T17:19:35Z | |
| dc.date.available | 2021-01-03T17:19:23Z | |
| dc.date.issued | 2018 | |
| dc.description.abstract | Viruses are among the most rapidly evolving entities in biology and are so intricately associated with their obligate hosts that the boundary between host and pathogen, and thus the study of one versus the other, is blurred by intimate interactions at scales ranging from proteins to populations. Viral genetic variation is both ecologically and molecularly determined, and thus viruses serve as measurably evolving populations that provide a window into adaptations and behaviors of their vertebrate hosts. Of all viral families, the biology of retroviruses is coupled especially tightly to that of the host due to permanent integration of viral DNA into eukaryotic chromosomes, producing an inherently dynamic infection that persists for life. Feline immunodeficiency virus (FIV) is among the oldest of viruses in the Lentivirus genus and puma (Puma concolor) are the most extensively ranging New World terrestrial mammal. We used molecular analyses to investigate the host-pathogen interactions between pumas and FIV across geographic and temporal space, within and across populations, and among FIV subtypes. In Chapter One, we investigate cross-species transmission of FIV from bobcats to pumas and compare the outcome of spillover infections in two populations separated by vast geographic space. Our findings reveal that the puma is typically a dead-end host of bobcat FIV infection, although altered population dynamics can promote stuttering chains of infection following spillover events. In Chapter Two, we employed a novel next generation sequencing technique to investigate the impact of management interactions such as population supplementation on FIV dynamics in the endangered Florida panther. Results from this chapter show evidence for cointroduction of one subtype of FIV with translocated pumas from Texas, followed by local extinction of the previously circulating, 'less fit' subtype in the puma host. Chapter Three describes an important intrinsic driver of viral evolution through characterization of the APOBEC3 protein A3Z3 in the puma, a primary cellular restriction factor against FIV. We show evidence that at least one geographically associated genotype of puma FIV is able to evade lethal hypermutation typical of A3Z3 activity despite a deficiency in the viral counter protein Vif. The collective findings of this work explore the ancient relationship between a vastly ranging apex predator and a chronic lentiviral infection by applying both novel and conventional methodologies to a unique, naturally occurring host-pathogen system. Although our questions were specific to FIV in pumas, the methodologies described here can be applied to other systems and models to address inherent limitations of opportunistic field studies including DNA degradation and sequencing of low copy number templates from archival biological samples. Ancient viral infections have the potential to elucidate the life history of mammalian hosts, which is particularly useful in the study of elusive and broadly ranging carnivores threatened by urbanization and habitat fragmentation. Future objectives of this work will expand analyses to incorporate additional populations, such as the modern Texas puma, and more thoroughly investigate genotype variation in Vif-A3Z3 interactions. Collectively, our results will inform additional studies that seek to elucidate determinants of host-pathogen interactions in naturally-occurring systems across diverse ecosystems and broad spatiotemporal scales. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | Malmberg_colostate_0053A_15215.pdf | |
| dc.identifier.uri | https://hdl.handle.net/10217/193179 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.subject | feline immunodeficiency virus | |
| dc.subject | lentiviral evolution | |
| dc.subject | restriction factors | |
| dc.subject | cross-species transmission | |
| dc.subject | puma | |
| dc.subject.lcsh | Florida panther | |
| dc.title | Extrinsic and intrinsic drivers of feline immunodeficiency virus evolution in the mountain lion | |
| dc.type | Text | |
| dcterms.embargo.expires | 2021-01-03 | |
| dcterms.embargo.terms | 2021-01-03 | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Microbiology, Immunology, and Pathology | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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