title: Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells.
abstract: Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.
authors: Department of Medicine, Section of Pulmonary Disease and Critical Care, Tulane University School of Medicine, New Orleans, LA, USA.
authors: Mark D
authors: MD
authors: Sides
authors: Gregory J
authors: GJ
authors: Block
authors: Bin
authors: B
authors: Shan
authors: Kyle C
authors: KC
authors: Esteves
authors: Zhen
authors: Z
authors: Lin
authors: Erik K
authors: EK
authors: Flemington
authors: Joseph A
authors: JA
authors: Lasky
references: Int J Cancer. 1999 Sep 24;83(1):121-6
references: 10449618
references: Virology. 2004 Sep 15;327(1):134-43
references: 15327904
references: J Virol. 2005 May;79(9):5875-9
references: 15827204
references: Cancer Treat Rev. 2009 Aug;35(5):425-30
references: 19464807
references: FEBS Lett. 2008 Sep 22;582(21-22):3174-8
references: 18708055
references: Oncogene. 1995 Sep 7;11(5):871-6
references: 7545807
references: Oncogene. 1995 Dec 21;11(12):2565-73
references: 8545113
references: J Biol Chem. 2004 Oct 29;279(44):46335-42
references: 15322136
references: J Virol. 2000 Dec;74(24):11800-10
references: 11090180
references: Mol Cell Biol. 2006 Dec;26(23):8814-25
references: 16966371
references: Gene Ther. 1995 Dec;2(10):702-9
references: 8750009
references: J Virol. 1990 Mar;64(3):1227-32
references: 2154606
references: Ann Hematol. 2004 Mar;83(3):198-200
references: 15064871
references: Cancer Res. 2006 Sep 1;66(17):8762-9
references: 16951192
references: Otolaryngol Head Neck Surg. 2004 Nov;131(5):651-4
references: 15523443
references: Nucleic Acids Res. 2005 Nov 27;33(21):e182
references: 16314296
references: J Am Acad Dermatol. 2005 Nov;53(5):890-2
references: 16243151
references: J Virol. 2010 Nov;84(21):11113-23
references: 20719947
references: Cancer Res. 2000 Oct 15;60(20):5781-8
references: 11059774
references: J Virol. 2004 Jan;78(2):868-81
references: 14694118
references: J Cell Biol. 1997 Jul 14;138(1):5-16
references: 9214377
references: Virus Res. 2006 May;117(2):244-53
references: 16307818
references: Antimicrob Agents Chemother. 2001 Jul;45(7):2082-91
references: 11408227
references: J Cell Sci. 2009 Aug 1;122(Pt 15):2613-22
references: 19567472
references: J Virol. 2001 Nov;75(22):10683-95
references: 11602710
references: J Gen Virol. 1988 Jun;69 ( Pt 6):1179-93
references: 2838570
references: Am J Pathol. 1993 Oct;143(4):1063-71
references: 8214002
references: Int J Cancer. 2010 May 15;126(10):2479-89
references: 19816947
references: Curr Opin Oncol. 2001 Sep;13(5):360-7
references: 11555713
references: Am J Pathol. 1991 Sep;139(3):469-74
references: 1653517
references: Clin Lymphoma Myeloma. 2006 Nov;7(3):192-8
references: 17229334
references: Clin Cancer Res. 2004 Feb 1;10(3):803-21
references: 14871955
references: EMBO J. 1994 Nov 1;13(21):5062-9
references: 7957072
references: Nat Rev Mol Cell Biol. 2007 Dec;8(12):1006-16
references: 17928811
references: Nat New Biol. 1973 Aug 22;244(138):245-7
references: 4353684
references: Cancer Res. 1999 Sep 1;59(17):4175-9
references: 10485449
references: Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):437-42
references: 11752411
references: Sci Sin. 1978 Jan-Feb;21(1):127-34
references: 206962
references: J Virol. 2001 Dec;75(24):12393-401
references: 11711629
references: J Gen Virol. 1994 Jun;75 ( Pt 6):1223-33
references: 8207389
references: J Cell Biol. 1996 Aug;134(4):815-26
references: 8769408
references: Cancer Res. 1993 Nov 1;53(21):5274-83
references: 8221662
references: Br J Dermatol. 1999 Dec;141(6):1106-9
references: 10606861
references: Cancer Res. 2002 Mar 15;62(6):1920-6
references: 11912175
references: Cancer. 1994 May 1;73(9):2239-49
references: 8168030
references: Trans Am Clin Climatol Assoc. 2006;117:55-73; discussion 73-4
references: 18528464
references: Oncogene. 1996 Nov 21;13(10):2243-54
references: 8950992
references: Virology. 1996 Mar 1;217(1):67-75
references: 8599237
references: Expert Rev Mol Med. 2007 May 04;9(12):1-24
references: 17477889
references: Proc Natl Acad Sci U S A. 1973 Nov;70(11):3265-8
references: 4361687
references: J Virol. 1993 May;67(5):2637-45
references: 8386269
references: Ann Otol Rhinol Laryngol. 1997 Apr;106(4):348-56
references: 9109729
references: Cancer Res. 2002 Jul 15;62(14):3893-903
references: 12124315
references: J Cell Sci. 2005 Mar 1;118(Pt 5):847-54
references: 15731002
references: Br J Dermatol. 2003 Oct;149(4):757-62
references: 14616366
references: Blood. 2008 Jan 15;111(2):566-73
references: 17959855
references: J Cancer Res Clin Oncol. 1994;120(5):303-8
references: 8126060
references: Blood Cells Mol Dis. 1998 Jun;24(2):114-23
references: 9628848
references: Int J Cancer. 1983 May 15;31(5):587-90
references: 6852976
references: Cancer Res. 2006 Aug 15;66(16):7999-8006
references: 16912175
references: Semin Cancer Biol. 2002 Dec;12(6):431-41
references: 12450729
references: J Natl Cancer Inst. 2004 Nov 17;96(22):1691-702
references: 15547182
references: J Clin Oncol. 2001 Sep 15;19(18):3852-60
references: 11559723
references: Trends Microbiol. 1997 Oct;5(10):399-405
references: 9351176
references: Cell. 1985 Dec;43(3 Pt 2):831-40
references: 3000618
references: J Biol Chem. 2008 Jul 25;283(30):21065-73
references: 18499657
references: Science. 2010 Apr 9;328(5975):240-3
references: 20378816
references: Mol Cell Biol. 1998 Aug;18(8):4899-913
references: 9671498
references: J Gen Virol. 1995 Nov;76 ( Pt 11):2887-93
references: 7595400
references: J Virol. 2010 May;84(9):4534-42
references: 20181711
references: Oncogene. 1992 Sep;7(9):1775-82
references: 1354347
references: J Virol. 2001 Mar;75(5):2388-99
references: 11160742
references: J Virol. 2004 Feb;78(4):1893-902
references: 14747554
references: J Cell Sci. 2003 Nov 1;116(Pt 21):4455-66
references: 13130097
references: Nature. 1995 Jun 22;375(6533):685-8
references: 7540727
references: J Clin Microbiol. 2003 Jun;41(6):2633-40
references: 12791891
references: J Drugs Dermatol. 2006 Feb;5(2):182-5
references: 16485889
references: J Virol. 2006 May;80(10):5078-81
references: 16641300
references: Mol Pathol. 2000 Oct;53(5):255-61
references: 11091849
references: Nat Cell Biol. 2008 May;10(5):547-55
references: 18408733
references: J Cell Biol. 2000 Jan 24;148(2):283-92
references: 10648561
references: Oncologist. 2002;7 Suppl 1:14-9
references: 11961205
references: J Cell Sci. 2006 Mar 15;119(Pt 6):1026-33
references: 16492708
references: PLoS Pathog. 2008 Oct 03;4(10):e1000170
references: 18833293
references: Cancer Lett. 2007 Mar 8;247(1):77-83
references: 16647201
references: Clin Cancer Res. 2010 Jun 1;16(11):3019-27
references: 20501625
references: Am J Respir Cell Mol Biol. 2011 Jun;44(6):852-62
references: 20693406