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Restriction of Human Polyomavirus BK Virus DNA Replication in Murine Cells and Extracts
Author(s)
Date Issued
2009-03-18
Date Available
2013-11-28T14:59:53Z
Abstract
BK virus (BKV) causes persistent and asymptomatic infections in most humans and is the etiologic agent of polyomavirus-associated nephropathy (PVAN) and other pathologies. Unfortunately, there are no animal models with which to study activation of BKV replication in the human kidney and the accompanying PVAN. Here we report studies of the restriction of BKV replication in murine cells and extracts and the cause(s) of this restriction. Upon infection of murine cells, BKV expressed large T antigen (TAg), but viral DNA replication and progeny were not detected. Transfection of murine cells with BKV TAg expression vectors also caused TAg expression without accompanying DNA replication. Analysis of the replication of DNAs containing chimeric BKV and murine polyomavirus origins revealed the importance of BKV core origin sequences and TAg for DNA replication. A sensitive assay was developed with purified BKV TAg that supported TAg-dependent BKV DNA replication with human but not with murine cell extracts. Addition of human replication proteins, DNA polymerase α-primase, replication protein A, or topoisomerase I to the murine extracts with BKV TAg did not rescue viral DNA replication. Notably, addition of murine extracts to human extracts inhibited BKV TAg-dependent DNA replication at a step prior to or during unwinding of the viral origin. These findings and differences in replication specificity between BKV TAg and the TAgs of simian virus 40 (SV40) and JC virus (JCV) and their respective origins implicate features of the BKV TAg and origin distinct from SV40 and JCV in restriction of BKV replication in murine cells.
Other Sponsorship
NIH grant R21 AI062848, INTAS, Health Research Board, Ireland, and Science Foundation Ireland grants NIH grant AI060584 and the F. G. Novy Fellowship
Type of Material
Journal Article
Publisher
American Society for Microbiology
Journal
Journal of Virology
Volume
83
Issue
11
Start Page
5708
End Page
5717
Copyright (Published Version)
2009 American Society for Microbiology
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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