Restriction of Human Polyomavirus BK Virus DNA Replication in Murine Cells and Extracts

DC FieldValueLanguage
dc.contributor.authorMahon, C.en
dc.contributor.authorLiang, B.en
dc.contributor.authorTikhanovich, I.en
dc.contributor.authoret al.en
dc.date.accessioned2013-11-28T14:59:53Z-
dc.date.available2013-11-28T14:59:53Z-
dc.date.copyright2009 American Society for Microbiologyen
dc.date.issued2009-03-18en
dc.identifier.citationJournal of Virologyen
dc.identifier.urihttp://hdl.handle.net/10197/5000-
dc.description.abstractBK 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.en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.subjectHuman Polyomavirusen
dc.subjectBK virus (BKV)en
dc.subjectDNA Replicationen
dc.titleRestriction of Human Polyomavirus BK Virus DNA Replication in Murine Cells and Extractsen
dc.typeJournal Articleen
dc.internal.availabilityFull text availableen
dc.statusPeer revieweden
dc.identifier.volume83en
dc.identifier.issue11en
dc.identifier.startpage5708en
dc.identifier.endpage5717en
dc.identifier.doi10.1128/JVI.00300-09-
dc.neeo.contributorMahon|C.|aut|-
dc.neeo.contributorLiang|B.|aut|-
dc.neeo.contributorTikhanovich|I.|aut|-
dc.neeo.contributoret al.||aut|-
dc.internal.notesPaper93.pdfen
dc.description.othersponsorshipNIH grant R21 AI062848, INTAS, Health Research Board, Ireland, and Science Foundation Ireland grants NIH grant AI060584 and the F. G. Novy Fellowshipen
dc.description.adminDeposited by bulk importen
dc.date.updated2013-11-27T16:35:50.274Zen
item.grantfulltextopen-
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