title: Kaposi's sarcoma-associated herpesvirus RTA activates the processivity factor ORF59 through interaction with RBP-Jkappa and a cis-acting RTA responsive element.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) displays two life modes, latency and lytic reactivation in the infected host cells which are equally important for virus mediated pathogenesis. During latency only a small number of genes are expressed. Under specific conditions, KSHV can undergo lytic replication with the production of viral progeny. One immediate-early gene RTA, encoded by open reading frame 50 of KSHV, has been shown to play a critical role in switching the viral latency to lytic reactivation. Over-expression of RTA from a heterologous promoter is sufficient for driving KSHV lytic replication which results in production of viral progeny. In the present study, we show that RTA can activate the expression of the ORF59 which encodes the processivity factor essential for DNA replication during lytic reactivation. We also show that RTA regulates ORF59 promoter through interaction with RBP-Jkappa as well as a cis-acting RTA responsive element within the promoter. In the context of KSHV infected cells, the upregulation of ORF59 is a direct response to RTA expression. Taken together, our findings provide new evidence to explain the mechanism by which RTA can regulate its downstream gene ORF59, further increasing our understanding of the biology of KSHV lytic replication.
authors.affiliation: Institut Pasteur of Shanghai, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai 200025, The People's Republic of China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Liu
authors.forename: Yajun
authors.initials: Y
authors.lastname: Cao
authors.forename: Deguang
authors.initials: D
authors.lastname: Liang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Erle S
authors.initials: ES
authors.lastname: Robertson
authors.forename: Ke
authors.initials: K
authors.lastname: Lan
mesh_terms: D000818:Animals; D002460:Cell Line; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D051379:Mice; D025941:Protein Interaction Mapping; D015534:Trans-Activators / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C110348:ORF59 protein, Human herpesvirus 8; C497570:RBPJ protein, human; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins
references.citation: J Virol. 2001 Aug;75(15):6894-900
references.pmid: 11435569
references.citation: Oncogene. 2003 Aug 11;22(33):5150-63
references.pmid: 12910252
references.citation: J Virol. 2003 Jan;77(1):600-23
references.pmid: 12477864
references.citation: Blood. 2001 May 15;97(10):3244-50
references.pmid: 11342455
references.citation: J Virol. 2000 Dec;74(23):10920-9
references.pmid: 11069986
references.citation: J Virol. 2003 Sep;77(17):9590-612
references.pmid: 12915572
references.citation: J Virol. 1998 Feb;72(2):1005-12
references.pmid: 9444993
references.citation: Genes Dev. 2002 Aug 1;16(15):1977-89
references.pmid: 12154127
references.citation: J Virol. 2001 Apr;75(7):3129-40
references.pmid: 11238840
references.citation: J Virol. 2005 Mar;79(6):3479-87
references.pmid: 15731242
references.citation: J Virol. 2002 Jan;76(2):802-16
references.pmid: 11752170
references.citation: J Virol. 2002 Apr;76(7):3168-78
references.pmid: 11884541
references.citation: Semin Cell Dev Biol. 1998 Dec;9(6):609-17
references.pmid: 9892565
references.citation: J Virol. 1999 Nov;73(11):9348-61
references.pmid: 10516043
references.citation: Arch Virol. 2001;146(2):403-13
references.pmid: 11315648
references.citation: Mol Cell Biol. 1990 Jan;10(1):165-75
references.pmid: 2294402
references.citation: J Virol. 2005 Mar;79(6):3468-78
references.pmid: 15731241
references.citation: Blood. 1995 Aug 15;86(4):1276-80
references.pmid: 7632932
references.citation: J Virol. 2001 Feb;75(3):1487-506
references.pmid: 11152521
references.citation: J Virol. 1997 Aug;71(8):5894-904
references.pmid: 9223479
references.citation: J Virol. 1998 Nov;72(11):8463-71
references.pmid: 9765382
references.citation: J Virol. 2000 Apr;74(7):3388-98
references.pmid: 10708456
references.citation: Virology. 1998 Dec 20;252(2):304-12
references.pmid: 9878608
references.citation: J Virol. 2005 Jun;79(12):7453-65
references.pmid: 15919901
references.citation: J Virol. 2002 Aug;76(16):8252-64
references.pmid: 12134031
references.citation: Curr Top Microbiol Immunol. 2007;312:71-100
references.pmid: 17089794
references.citation: Nature. 1988 Oct 6;335(6190):563-4
references.pmid: 3047590
references.citation: J Virol. 2003 Jun;77(12):6761-8
references.pmid: 12767996
references.citation: J Virol. 1998 Oct;72(10):8309-15
references.pmid: 9733875
references.citation: Nat Genet. 2003 Mar;33(3):401-6
references.pmid: 12590264
references.citation: Genes Dev. 1999 Dec 15;13(24):3217-30
references.pmid: 10617571
references.citation: J Virol. 1992 Aug;66(8):5047-58
references.pmid: 1321287
references.citation: J Virol. 2004 Jun;78(12):6585-94
references.pmid: 15163750
references.citation: J Virol. 2001 Aug;75(15):6786-99
references.pmid: 11435557
references.citation: N Engl J Med. 1995 May 4;332(18):1186-91
references.pmid: 7700311
references.citation: J Virol. 1999 Mar;73(3):2232-42
references.pmid: 9971806
references.citation: J Virol. 2000 Jul;74(13):6207-12
references.pmid: 10846108
references.citation: Int J Cancer. 1996 Jan 3;65(1):25-8
references.pmid: 8543391
references.citation: Curr Opin Genet Dev. 2000 Aug;10(4):363-9
references.pmid: 10889061
references.citation: Virology. 2004 Jan 20;318(2):542-55
references.pmid: 14972523
references.citation: Nat Med. 1996 Mar;2(3):342-6
references.pmid: 8612236
references.citation: J Virol. 2007 Jun;81(11):5788-806
references.pmid: 17392367
references.citation: J Virol. 2003 Apr;77(7):4205-20
references.pmid: 12634378
references.citation: Virology. 1998 Jan 5;240(1):118-26
references.pmid: 9448696
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10866-71
references.pmid: 9724796
references.citation: Virology. 2005 Sep 30;340(2):183-91
references.pmid: 16043206
references.citation: J Virol. 2007 Feb;81(3):1062-71
references.pmid: 17108026
references.citation: J Virol. 1998 Jul;72(7):6228-32
references.pmid: 9621095
references.citation: J Gen Virol. 1999 Jan;80 ( Pt 1):83-90
references.pmid: 9934688
references.citation: Infect Agents Dis. 1996 Oct;5(4):215-22
references.pmid: 8884366
references.citation: Curr Top Microbiol Immunol. 2007;312:157-83
references.pmid: 17089797
references.citation: J Virol. 1996 Jan;70(1):549-58
references.pmid: 8523568
references.citation: J Biol Chem. 2004 Jul 2;279(27):28375-86
references.pmid: 15075322
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14862-7
references.pmid: 8962146
references.citation: Science. 1994 Dec 16;266(5192):1865-9
references.pmid: 7997879