Elucidating the molecular determinants of vector tropism of Uukuniemi virus

Wilson, Alexandra (2024) Elucidating the molecular determinants of vector tropism of Uukuniemi virus. PhD thesis, University of Glasgow.

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Ticks are vectors capable of transmitting viruses, such as those within the order Bunyavirales. These interactions between virus and vector are severely understudied, despite ticks and the viruses they transmit posing an ever-increasing risk to human and animal health. Once exposed, ticks can be persistently infected, capable of transmitting the virus to other hosts for the duration of their lifespan and in some cases can pass on the virus to any offspring through vertical transmission. Additionally, as the impact of climate change increases, the abundance, activity window and geographical reach of ticks is expanding, further increasing the risk of exposure to the viruses they carry.

Over the last 80 years, the emergence and re-emergence of tick-borne bunyaviruses has led to several epidemics, with the mortality of some of these virus species exceeding 30%. However, as it stands, little information is known about the factors which dictate the vector specificity of these viruses, and the intracellular interactions within the tick that allow for persistent infection to be established. The work carried out within this thesis aims to begin tackling both gaps within our understanding. By using Uukuniemi virus (UUKV) as a model bunyavirus, the vector specificity of UUKV for ticks is confirmed and the stage at which viral replication is unable to proceed in non-vector arthropod cells has been identified. This work highlights the interactions within vector and non-vector arthropod cells in order to determine the requirements needed for UUKV to overcome this transmission barrier and demonstrates UUKV is unable to infect and replicate in cell lines derived from mosquitoes but readily infects human and tick cell cultures. In tandem with these findings, this work also presents the first tick cell line-derived RNA binding proteome (RBPome), achieved by using a cell line from the tick species Ixodes scapularis. The work also elucidates RNA binding proteins that are significantly differentially expressed during UUKV infection. As this methodology employs the use of RNA interactome capture through UV crosslinking and oligo(dT) capture beads to isolate samples for mass-spectrometry, the proteins highlighted in these findings reflect changes of activity within the cell as opposed to changes in overall protein abundance, as is seen with classical whole cell proteomics. Further biochemical analysis and downstream validation through dsRNA transfections to achieve gene knockdowns gives insights into both the makeup of the ISE6 cell line derived RBPome and preliminary insights into the importance of these proteins in viral replication kinetics. In summary, this work lays the foundations to elucidating the molecular determinants of Uukuniemi virus tropism within vector cells, alongside providing novel data on the intracellular landscape of the ISE6 cell line RBPome in naïve and rUUKV-infected conditions.

Item Type: Thesis (PhD)
Subjects: Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Supervisor's Name: Brennan, Dr. Ben and Castello, Professor Alfredo
Date of Award: 2024
Depositing User: Theses Team
Unique ID: glathesis:2024-84239
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 15 Apr 2024 15:54
Last Modified: 16 Apr 2024 08:20
Thesis DOI: 10.5525/gla.thesis.84239
URI: https://theses.gla.ac.uk/id/eprint/84239

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