title: miRNA regulation of BK polyomavirus replication during early infection.
abstract: Viral microRNAs (miRNAs) play an important role during infection by posttranscriptionally regulating both host and viral gene expression. However, the function of many viral miRNAs remains poorly understood. In this study, we investigated the role of the BK polyomavirus (BKPyV) miRNA in regulating virus replication. The function of the polyomavirus miRNA was investigated in archetype BKPyV, which is the transmissible form of the virus and thought to establish a persistent infection in the host urinary tract. In agreement with previous studies, we show that the BKPyV miRNA targets early mRNAs. Importantly, we show that the miRNA plays a significant role in limiting archetype BKPyV replication in a natural host cell model of infection. This regulation is accomplished through the balance of regulatory elements located within the noncoding control region that control early gene expression and miRNA expression before genome replication. We therefore provide evidence for a unique function of the polyomavirus miRNA that may have important implications for the mechanism of viral persistence.
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Nicole M
authors: NM
authors: Broekema
authors: Michael J
authors: MJ
authors: Imperiale
mesh_terms: D001739:BK Virus / Q000235:genetics* / Q000502:physiology; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D027601:Polyomavirus Infections / Q000821:virology*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000166:cytology; D014779:Virus Replication / Q000235:genetics
chemical_list: D004279:DNA, Viral; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral
references: Adv Exp Med Biol. 2006;577:1-18
references: 16626024
references: Virology. 2012 Jan 20;422(2):235-41
references: 22099377
references: J Mol Biol. 1967 Jun 14;26(2):365-9
references: 4291934
references: Virology. 2010 Nov 25;407(2):368-73
references: 20869740
references: Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
references: 12824337
references: J Virol. 2009 Feb;83(3):1350-8
references: 19036822
references: J Virol. 2010 Mar;84(6):2697-706
references: 20071580
references: Cell. 2007 Jun 29;129(7):1401-14
references: 17604727
references: Virology. 2011 Mar 15;411(2):325-43
references: 21277611
references: mBio. 2011 Feb 08;2(1):e00281-10
references: 21304169
references: Plant Methods. 2007 Oct 12;3:12
references: 17931426
references: Virus Genes. 1995;10(3):261-75
references: 8560788
references: Methods Mol Biol. 2011;721:153-71
references: 21431684
references: Nat Cell Biol. 2010 Feb;12(2):193-9
references: 20081837
references: Virology. 2004 Jun 1;323(2):182-8
references: 15193914
references: J Virol. 2008 Oct;82(20):9823-8
references: 18684810
references: J Med Virol. 1981;8(2):143-50
references: 6271922
references: Virology. 2009 Apr 25;387(1):157-67
references: 19272626
references: Cell Host Microbe. 2008 Jun 12;3(6):375-87
references: 18541214
references: EMBO Rep. 2010 Oct;11(10):784-90
references: 20847741
references: J Virol. 2007 Jan;81(1):272-9
references: 17035315
references: Nucleic Acids Res. 2005 Nov 27;33(20):e179
references: 16314309
references: Virology. 2005 Jan 20;331(2):209-31
references: 15629766
references: Virology. 2009 Jan 20;383(2):183-7
references: 19046593
references: J Gen Virol. 1977 Jul;36(1):59-74
references: 886304
references: Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3077-82
references: 22308400
references: Nature. 2005 Jun 2;435(7042):682-6
references: 15931223
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: J Virol. 1981 Sep;39(3):861-9
references: 6169844
references: Virology. 2009 Feb 20;384(2):352-9
references: 19101707
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Cell Host Microbe. 2011 Feb 17;9(2):93-102
references: 21320692
references: Nature. 2008 Sep 4;455(7209):64-71
references: 18668037
references: J Virol. 2004 Jan;78(2):751-7
references: 14694107
references: J Exp Med. 2008 Apr 14;205(4):841-52
references: 18347101