The kaposin RNA transcript is the architect of a successful Kaposi’s sarcoma-associated herpesvirus infection
| dc.contributor.advisor | Corcoran, Jennifer | |
| dc.contributor.author | Kleer, Mariel | |
| dc.contributor.committeemember | Lees-Miller, Susan | |
| dc.contributor.committeemember | Marle, Guido van | |
| dc.date | 2025-02 | |
| dc.date.accessioned | 2024-12-18T20:18:50Z | |
| dc.date.available | 2024-12-18T20:18:50Z | |
| dc.date.issued | 2024-12-11 | |
| dc.description.abstract | Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified in 1994 as the causative agent of the endothelial cell neoplasm, Kaposi’s sarcoma (KS). Soon after its discovery, the KSHV genome was found to code for an unusual viral RNA that was GC-rich, highly repetitive, and polycistronic, called kaposin. Kaposin is expressed during all phases of viral replication and is the most abundant viral transcript expressed in KS tumours; this makes the function of kaposin of great interest. However, in contrast to many other KSHV genes, the complex nature of kaposin impeded its study and its function during KSHV infection remains unknown. To address this, the Corcoran lab developed a set of recombinant viruses designed to eliminate kaposin protein expression both individually and in combination: ΔKapABC, ΔKapBC, ΔKapB, and ΔKapC. I describe the characterization of this set of recombinant viruses for the first time. I established cell lines stably infected with each kaposin-recombinant virus to permit their analysis, a valuable tool for the field. I used the ΔKapB virus to demonstrate that KapB, and not KapA or KapC, is required for the disassembly of cytoplasmic granules called processing bodies during KSHV infection. Unexpectedly, I found that all kaposin-recombinant viruses exhibit deficiencies in viral replication relative to the wildtype KSHV control. As each recombinant virus encodes a unique repertoire of Kap proteins, but all have an altered primary nucleotide sequence, I hypothesized that the kaposin RNA itself has biological function. My subsequent work confirms this hypothesis in two ways; first, by demonstrating that kaposin transcription leads to the formation of a three-stranded nucleotide structure called an R-loop and second, by revealing that kaposin is a viral architectural RNA that can seed and remodel cellular nuclear bodies, called nuclear speckles, to optimize viral gene expression. Taken together, my thesis work represents the first in-depth analysis of kaposin function during KSHV infection. Beyond its protein coding capacity, I have demonstrated that this singular RNA has at least two additional functions: i) R-loop formation, and ii) nuclear speckle remodeling. These findings alter the longstanding assumptions of the KSHV field and have important implications for KS-associated disease. | |
| dc.identifier.citation | Last name, A. (YYYY). The kaposin RNA transcript is the architect of a successful Kaposi’s sarcoma-associated herpesvirus infection (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | |
| dc.identifier.uri | https://hdl.handle.net/1880/120199 | |
| dc.language.iso | en | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | virus RNA cancer | |
| dc.subject.classification | Microbiology | |
| dc.subject.classification | Biology--Molecular | |
| dc.title | The kaposin RNA transcript is the architect of a successful Kaposi’s sarcoma-associated herpesvirus infection | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Medicine – Microbiology & Infectious Diseases | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.thesis.accesssetbystudent | I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible. |