Induction of cellular stress overcomes the requirement of herpes simplex virus type 1 for immediate-early protein ICP0 and reactivates expression from quiescent viral genomes.
Herpes simplex virus type 1 (HSV-1) mutants impaired in the activities of the structural protein VP16 and the immediate-early (IE) proteins ICP0 and ICP4 establish a quiescent infection in human fibroblasts, with most cells retaining an inactive, repressed viral genome for sustained periods in culture. To date, the quiescent state has been considered stable, since it has been reversed only by provision of herpesviral proteins, such as ICP0, not by alteration of the cell physiological state. We report that the interaction of HSV-1 with human fibroblasts can be altered significantly by transient treatment of cultures with sodium arsenite, an inducer of heat shock and oxidative stress, or gramicidin D, a toxin that selectively permeabilizes cell membranes, prior to infection. These regimens stimulated gene expression from IE-deficient HSV-1 mutants in a promoter sequence-independent manner and also overcame the replication defect of ICP0-null mutants. Reactivation of gene expression from quiescent HSV-1 genomes and the resumption of virus replication were observed following addition of arsenite or gramicidin D to cultures. Both agents induced reorganization of nuclear domain 10 structures, the sites of quiescent genomes, but appeared to do so through different mechanisms. The results demonstrate that the physiological state of the cell is important in determining the outcome of infection with IE-deficient HSV-1 and show novel methods for reactivating quiescent HSV-1 in fibroblasts with a high efficiency.
Preston
Chris M
CM
Medical Research Council Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom. c.preston@mrcvu.gla.ac.uk
Nicholl
Mary Jane
MJ
D017209:Apoptosis; D018053:Arsenites / Q000494:pharmacology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics; D017781:Genes, Immediate-Early; D016679:Genome, Viral; D006096:Gramicidin / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D014775:Virus Activation
D018053:Arsenites; D017874:Immediate-Early Proteins; D006096:Gramicidin; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; C015001:arsenite
J Gen Virol. 1998 Jan;79 ( Pt 1):117-24
9460932
Mol Cell Biol. 2006 Dec;26(23):8814-25
16966371
Exp Cell Res. 2003 Feb 1;283(1):1-16
12565815
Carcinogenesis. 2002 May;23(5):867-76
12016162
J Virol. 2006 May;80(9):4528-37
16611913
J Gen Virol. 1984 May;65 ( Pt 5):859-63
6327885
J Virol. 1992 Apr;66(4):2150-6
1312625
J Virol. 2006 Apr;80(7):3360-8
16537603
J Virol. 2001 Apr;75(8):3885-95
11264377
Trends Biochem Sci. 2003 Jun;28(6):294-304
12826401
J Gen Virol. 1995 Jun;76 ( Pt 6):1417-31
7782770
J Neurosci. 1990 Apr;10(4):1268-75
2158529
J Virol. 1995 Oct;69(10):6249-58
7666525
Clin Microbiol Rev. 2003 Jan;16(1):79-95
12525426
J Virol. 1998 Apr;72(4):3307-20
9525658
Am J Physiol Cell Physiol. 2000 Jun;278(6):C1116-25
10837339
Virol J. 2005 Nov 21;2:85
16300675
J Virol. 2007 Oct;81(20):10991-1004
17670833
J Gen Virol. 1989 May;70 ( Pt 5):1185-202
2543774
Carcinogenesis. 2003 Apr;24(4):747-56
12727804
J Virol. 2008 Mar;82(5):2339-49
18094162
J Neurovirol. 2005 Jul;11(3):306-17
16036811
J Virol. 2008 Mar;82(6):2661-72
18160441
J Virol. 1987 Mar;61(3):829-39
3027408
J Virol. 2001 Jan;75(2):750-8
11134288
J Virol. 2004 Feb;78(4):1763-74
14747541
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7408-12
2823260
Biochim Biophys Acta. 2007 Sep;1768(9):2011-25
17572379
J Virol. 1985 Mar;53(3):751-60
2983086
EMBO J. 1994 Nov 1;13(21):5062-9
7957072
Bioessays. 2000 Aug;22(8):761-70
10918307
Biochem J. 2004 Sep 1;382(Pt 2):641-50
15175009
J Gen Virol. 1997 Jul;78 ( Pt 7):1653-61
9225042
J Virol. 1996 Aug;70(8):5051-60
8764012
EMBO J. 1998 Dec 15;17(24):7161-9
9857173
Virology. 1983 May;127(1):159-67
6305013
Virology. 1992 May;188(1):311-8
1314458
J Virol. 2006 Jun;80(12):6188-91
16731959
J Virol. 1979 Jan;29(1):275-84
219222
Curr Eye Res. 1986 Mar;5(3):241-6
3009094
J Virol. 2007 Nov;81(21):11781-9
17715242
J Virol. 1999 Oct;73(10):8512-8
10482604
Genes Dev. 2006 Jan 1;20(1):1-15
16391229
J Virol. 2008 Jan;82(1):126-37
17942542
J Virol. 2004 Jun;78(12):6162-70
15163709
Infect Immun. 1980 Sep;29(3):902-7
6253401
J Virol. 2005 Apr;79(8):5078-89
15795293
J Gen Virol. 1992 Feb;73 ( Pt 2):285-92
1371540
J Virol. 2004 Mar;78(5):2169-78
14963113
J Gen Virol. 1986 Dec;67 ( Pt 12):2571-85
3025339
J Virol. 1997 Oct;71(10):7807-13
9311867
Mol Cell Biol. 1996 Jun;16(6):3085-93
8649420
J Virol. 1998 Aug;72(8):6581-91
9658103
J Virol. 1991 Aug;65(8):4078-90
1649316
Biochem J. 2002 Aug 1;365(Pt 3):639-48
11964141
Toxicol Appl Pharmacol. 2001 May 1;172(3):249-61
11312654
J Cell Physiol. 2006 May;207(2):562-9
16447264
EMBO J. 1984 Dec 20;3(13):3135-41
6098466
J Virol. 2001 Apr;75(7):3391-403
11238865
J Virol. 2006 Apr;80(8):3863-71
16571803
Biochim Biophys Acta. 1991 Nov 4;1069(2):201-8
1718432
Virology. 2006 Aug 15;352(1):237-52
16750236
EMBO J. 1999 Mar 15;18(6):1526-38
10075924
J Gen Virol. 2002 Jul;83(Pt 7):1601-1612
12075078
Bioessays. 2000 Mar;22(3):227-34
10684582
Virus Genes. 2006 Oct;33(2):163-7
16972030
Clin Microbiol Rev. 1997 Jul;10(3):419-43
9227860
Virus Res. 2005 Aug;111(2):108-19
15951043
J Membr Biol. 1985;83(3):251-9
3999123
J Virol. 2006 Apr;80(7):3650-4
16537633
J Virol. 2006 Aug;80(16):7995-8005
16873256
J Virol. 1999 May;73(5):4171-80
10196313
J Virol. 2007 Jun;81(11):6106-10
17360760
Arch Virol. 1997;142(11):2225-35
9672588
J Virol. 2006 Nov;80(22):10919-30
16943285
J Gen Virol. 1989 Mar;70 ( Pt 3):695-704
2543754
J Gen Virol. 2006 May;87(Pt 5):1113-1121
16603511
J Virol. 2005 Jan;79(1):525-35
15596845
J Virol. 2002 Jan;76(2):841-50
11752173
J Virol. 2007 Nov;81(22):12394-405
17855552