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Identification of BK Polyomavirus Agnoprotein as a Novel Viroporin

Swinscoe, Gemma Ede (2019) Identification of BK Polyomavirus Agnoprotein as a Novel Viroporin. PhD thesis, University of Leeds.

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Abstract

BK polyomavirus (BKPyV) is a small dsDNA virus and a common opportunistic infection in kidney transplant patients where it causes polyomavirus associated nephropathy (PVAN). In addition to the standard complement of structural and non- structural proteins, BKPyV also encodes a small auxiliary protein termed the agnoprotein. This is a small, highly basic protein that is expressed late during the viral life cycle. Previous studies have shown that agnoprotein is a novel viral egress factor. Polyomaviruses lacking agnoprotein show a profound defect in virus release into cell culture media. Despite these observations the mechanism by which the agnoprotein regulates such a critical stage in the viral lifecycle is poorly understood. In 2010, the agnoprotein encoded for by JC polyomavirus (JCPyV) was shown to have a viroporin function. Viroporins are a family of virally encoded channel forming proteins, which are well characterised to have essential functions during virus egress. Viroporins have become ubiquitous across many viral families and popular drug targets in many cases. We have developed a detergent-free purification system for the production of recombinant BKPyV agnoprotein. Using this system, we have been able to show that this viroporin function is conserved in BKPyV and that the channel formed is sensitive to classical viroporin inhibitors.

Item Type: Thesis (PhD)
Keywords: BK Polyomavirus, Viroporin, Agnoprotein
Academic Units: The University of Leeds > University of Leeds Research Centres and Institutes > Astbury Centre for Structural Molecular Biology (Leeds)
The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute for Molecular and Cellular Biology (Leeds)
Depositing User: Miss G E Swinscoe
Date Deposited: 12 May 2020 16:21
Last Modified: 12 May 2020 16:21
URI: http://etheses.whiterose.ac.uk/id/eprint/26806

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