Investigating the mechanisms of BK Polyomavirus egress and virus-host interactions.
type: CreativeWork
description: BK polyomavirus (BKPyV) is a small, non-enveloped dsDNA virus that infects 70 – 90% of the world’s population and causes a lifelong, silently persistent infection. In immunocompromised individuals, BKPyV replication can result in serious pathology. Bone marrow transplant patients can develop haemorrhagic cystitis, and in kidney transplant patients BKPyV replication can provoke a nephropathy that leads to deterioration of allograft function and eventual loss of the transplanted organ. There are currently no antiviral treatments with clinical efficacy against BKPyV-associated nephropathy. The relatively small viral genome and paucity of viral proteins produced by BKPyV suggests a significant reliance on the host for viral life cycle progression. However, the lack of effective antiviral treatments indicates an incomplete understanding of such virus-host interactions. Therefore, this thesis aimed to uncover novel virus-host interactions by following up the results of a high- throughput, genome-wide loss-of-function CRISPR screen, which led to the discovery of S-adenosylmethionine transferase MAT2A as a potentially important factor in early viral life cycle progression. The results presented here reveal that deletion of MAT2A results in the reduction of infected cell number and several early viral life cycle phenotypes. The mechanism behind the influence of MAT2A in the early viral life is likely to be partly due to the effect of MAT2A on cell cycle status, previously determined to have a significant effect on viral life cycle progression. Additionally, while the life cycles of non-enveloped viruses are often assumed to require cell lysis to release progeny virions, the lack of resultant acute inflammatory responses in asymptomatically infected, immunocompetent individuals implies that BKPyV may utilize a more surreptitious method of dissemination. Indeed, there is increasing evidence to suggest that BKPyV exits the cell via non-lytic means using an unconventional secret…
abstract: BK polyomavirus (BKPyV) is a small, non-enveloped dsDNA virus that infects 70 – 90% of the world’s population and causes a lifelong, silently persistent infection. In immunocompromised individuals, BKPyV replication can result in serious pathology. Bone marrow transplant patients can develop haemorrhagic cystitis, and in kidney transplant patients BKPyV replication can provoke a nephropathy that leads to deterioration of allograft function and eventual loss of the transplanted organ. There are currently no antiviral treatments with clinical efficacy against BKPyV-associated nephropathy. The relatively small viral genome and paucity of viral proteins produced by BKPyV suggests a significant reliance on the host for viral life cycle progression. However, the lack of effective antiviral treatments indicates an incomplete understanding of such virus-host interactions. Therefore, this thesis aimed to uncover novel virus-host interactions by following up the results of a high- throughput, genome-wide loss-of-function CRISPR screen, which led to the discovery of S-adenosylmethionine transferase MAT2A as a potentially important factor in early viral life cycle progression. The results presented here reveal that deletion of MAT2A results in the reduction of infected cell number and several early viral life cycle phenotypes. The mechanism behind the influence of MAT2A in the early viral life is likely to be partly due to the effect of MAT2A on cell cycle status, previously determined to have a significant effect on viral life cycle progression. Additionally, while the life cycles of non-enveloped viruses are often assumed to require cell lysis to release progeny virions, the lack of resultant acute inflammatory responses in asymptomatically infected, immunocompetent individuals implies that BKPyV may utilize a more surreptitious method of dissemination. Indeed, there is increasing evidence to suggest that BKPyV exits the cell via non-lytic means using an unconventional secret…
author: Ho, Sophia
language: eng
keywords: Virology, Molecular Biology, Microbiology, BK Polyomavirus
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2021-09-30
date modified: 2026-07-22T22:24:07Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.81153