The Herpes Simplex Virus-1 Transactivator Infected Cell Protein-4 Drives VEGF-A Dependent Neovascularization
Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes.
Vyšlo v časopise:
The Herpes Simplex Virus-1 Transactivator Infected Cell Protein-4 Drives VEGF-A Dependent Neovascularization. PLoS Pathog 7(10): e32767. doi:10.1371/journal.ppat.1002278
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002278
Souhrn
Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes.
Zdroje
1. HowardMSellorsJWJangDRobinsonNJFearonM 2003 Regional distribution of antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 in men and women in Ontario, Canada. J Clin Microbiol 41 84 89
2. LookerKJGarnettGP 2005 A systematic review of the epidemiology and interaction of herpes simplex virus types 1 and 2. Sex Transm Infect 81 103 107
3. MillerCSDanaherRJJacobRJ 1998 Molecular aspects of herpes simplex virus I latency, reactivation, and recurrence. Crit Rev Oral Biol Med 9 541 562
4. JamesSHKimberlinDWWhitleyRJ 2009 Antiviral therapy for herpesvirus central nervous system infections: neonatal herpes simplex virus infection, herpes simplex encephalitis, and congenital cytomegalovirus infection. Antiviral Res 83 210 213
5. GarciaDDShteinRMMuschDCElnerVM 2009 Herpes simplex virus keratitis: histopathologic neovascularization and corneal allograft failure. Cornea 28 963 965
6. ChongEMDanaMR 2008 Graft failure IV. Immunologic mechanisms of corneal transplant rejection. Int Ophthalmol 28 209 222
7. CursiefenCChenLBorgesLPJacksonDCaoJ 2004 VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 113 1040 1050
8. MasliSTurpieBStreileinJW 2006 Thrombospondin orchestrates the tolerance-promoting properties of TGFbeta-treated antigen-presenting cells. Int Immunol 18 689 699
9. CueniLNDetmarM 2008 The lymphatic system in health and disease. Lymphat Res Biol 6 109 122
10. CursiefenCChenLDanaMRStreileinJW 2003 Corneal lymphangiogenesis: evidence, mechanisms, and implications for corneal transplant immunology. Cornea 22 273 281
11. YamagamiSDanaMRTsuruT 2002 Draining lymph nodes play an essential role in alloimmunity generated in response to high-risk corneal transplantation. Cornea 21 405 409
12. WuestTRCarrDJ 2010 VEGF-A expression by HSV-1-infected cells drives corneal lymphangiogenesis. J Exp Med 210 101 115
13. HarperSJBatesDO 2008 VEGF-A splicing: the key to anti-angiogenic therapeutics? Nature Rev Cancer 8 880 887
14. WirzeniusMTammelaTUutelaMHeYOdorisioT 2007 Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med 207 1441 1440
15. GongYKohDR 2010 Neutrophils promote inflammatory angiogenesis via release of preformed VEGF in an in vivo corneal model. Cell Tissue Res 339 437 48
16. KataruRPJungKJangCYangHSchwendenerRA 2009 Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution. Blood 113 5650 5659
17. SpirigRDjafarzadehSRegueiraTShawSGvon GarnierC 2010 Effects of TLR agonists on the hypoxia-regulated transcription factor HIF-1alpha and dendritic cell maturation under normoxic conditions. PLoS One 5 e0010983
18. Martinez-MartinNViejo-BorbollaA 2010 Toll-like receptor-mediated recognition of herpes simplex virus. Front Biosci 2 718 729
19. BeutlerB 2004 Inferences, questions and possibilities in Toll-like receptor signaling. Nature 430 257 263
20. BerraEPagesGPouyssegurJ 2000 MAP kinases and hypoxia in the control of VEGF expression. Cancer Metastasis Rev 19 139 145
21. BoteroTMSonJSVodopyanovDHasegawaMShelburneCE 2010 MAPK signaling is required for LPS-induced VEGF in pulp stem cells. J Dent Res 89 264 269
22. PagèsGPouysségurJ 2005 Transcriptional regulation of the vascular endothelial growth factor gene-A concert of activating factors. Cardiovasc Res 65 564 573
23. StrowskiMZCramerTSchäferGJüttnerSWalduckA 2004 Helicobacter pylori stimulates host vascular endothelial growth factor-A (vegf-A) gene expression via MEK/ERK-dependent activation of Sp1 and Sp3. FASEB J 18 221 220
24. HargettDMcLeanTBachenheimerSL 2005 Herpes simplex virus ICP27 activation of stress kinases JNK and p38. J Virol 79 8348 8360
25. PerkinsDPereiraEFGoberMYarowskyPJAurelianL 2002 The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) blocks apoptosis in hippocampal neurons, involving activation of the MEK/MAPK survival pathway. J Virol 76 1445 1449
26. ChenSHYaoHWChenITShiehBLiC 2008 Suppression of transcription factor early growth response 1 reduces herpes simplex virus lethality in mice. J Clin Invest 118 3470 3477
27. PavletichNPPaboCA 1991 Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science 252 809 817
28. NathansDChristyB 1989 DNA binding site of the growth factor-inducible protein Zif268. Proc Nat Acad Sci 86 8737 8741
29. RaychowdhuryRSchäferGFlemingJRosewiczSWiedenmannB 2002 Interaction of early growth response protein 1 (Egr-1), specificity protein 1 (Sp1), and cyclic adenosine 3′5′-monophosphate response element binding protein (CREB) at a proximal response element is critical for gastrin-dependent activation of the chromogranin A promoter. Mol Endocrinol 16 2802 2818
30. JohnsonPAEverettRD 1986 DNA replication is required for abundant expression of a plasmid-borne late US11 gene of herpes simplex virus type 1. Nucleic Acids Res 14 3609 3625
31. JohnsonPAMacLeanCMarsdenHSDalzielRGEverettRD 1986 The product of gene US11 of herpes simplex virus type 1 is expressed as a true late gene. J Gen Virol 67 871 883
32. DeLucaNASchafferPA 1988 Physical and functional domains of the herpes simplex virus transcriptional regulatory protein ICP4. J Virol 62 732 743
33. MalikAKMartinezRMuncyLCarmichaelEPWellerSK 1992 Genetic analysis of the herpes simplex virus type 1 UL9 gene: isolation of a lacZ insertion mutant and expression in eukaryotic cells. Virology 190 702 715
34. LeibDAHarrisonTELasloKMMachalekMAMoormanNJVirginHW 1999 Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. J Exp Med 189 663 72
35. RiceSAKnipeDM 1990 Genetic evidence for two distinct transactivation functions of the herpes simplex virus alpha protein ICP27. J Virol 64 1704 1715
36. SamaniegoLAWebbALDeLucaNA 1995 Functional interactions between herpes simplex virus immediate-early proteins during infection: gene expression as a consequence of ICP27 and different domains of ICP4. J Virol 69 5705 5715
37. XiaKDeLucaNAKnipeDM 1996 Analysis of phosphorylation sites of herpes simplex virus type 1 ICP4. J Virol 70 1061 1071
38. ImbalzanoANCoenDMDeLucaNA 1991 Herpes simplex virus transactivator ICP4 operationally substitutes for the cellular transcription factor Sp1 for efficient expression of the viral thymidine kinase gene. J Virol 65 565 574
39. PanagiotidisCALiumEKSilversteinSJ 1997 Physical and functional interactions between herpes simplex virus immediate-early proteins ICP4 and ICP27. J Virol 71 1547 1557
40. SampathPDelucaNA 2008 Binding of ICP4, TATA-binding protein, and RNA polymerase II to herpes simplex virus type 1 immediate-early, early, and late promoters in virus-infected cells. J Virol 82 2339 2349
41. HazlettLDHendricksRL 2010 Reviews for immune privilege in the year 2010: immune privilege and infection. Ocul Immunol Inflamm 18 237 243
42. BiswasPSBanerjeeKKinchingtonPRRouseBT 2006 Involvement of IL-6 in the paracrine production of VEGF in ocular HSV-1 infection. Exp Eye Res 82 46 54
43. Pinhal-EnfieldGRamanathanMHaskoGVogelSNSalzmanAL 2003 An angiogenic switch in macrophagesinvolving synergy between Toll-like receptors 2, 4, 7, and 9 and adenosine A(2A) receptors. Am J Pathol 163 711 721
44. KoffJLShaoMXUekiIFNadelJA 2008 Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. Am J Physiol Lung Cell Mol Physiol 294 L1068 L1075
45. GeorgelPJiangZKunzSJanssenEMolsJ 2007 Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway. Virology 362 304 313
46. LangKSNavariniAARecherMLangPAHeikenwalderM 2007 MyD88 protects from lethal encephalitis during infection with vesicular stomatitis virus. Eur J Immunol 37 2434 2440
47. YangPAnHLiuXWenMZhengY 2010 The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway. Nat Immunol 11 487 494
48. FurrSRMoerdyk-SchauweckerMGrdzelishviliVZMarriottI 2010 RIG-I mediates nonsegmented negative-sense RNA virus-induced inflammatory immune responses of primary human astrocytes. Glia 58 1620 1629
49. ZhangSYJouanguyEUgoliniSSmahiAElainG 2007 TLR3 deficiencyin patients with herpes simplex encephalitis. Science 317 1522 1527
50. KleinmanMEYamadaKTakedaAChandrasekaranVNozakiM 2008 Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452 591 597
51. PerryAKChenGZhengDTangHChengG 2005 The host type I interferon response to viral and bacterial infections. Cell Res 15 407 22
52. BrennanKBowieAG 2010 Activation of host pattern recognition receptors by viruses. Curr Opin Microbiol 13 503 507
53. MimuraKKonoKTakahashiAKawaguchiYFujiiH 2007 Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. Cancer Immunol Immunother 56 761 770
54. YuCQZhangMMatisKIKimCRosenblattMI 2008 Vascular endothelial growth factor mediates corneal nerve repair. Invest Ophthalmol Vis Sci 49 3870 3878
55. SmithCASchafferPA 1987 Intertypic recombinants of herpes simplex virus types 1 and 2 infected-cell polypeptide 4. Virology 160 176 182
56. IwahoriSShirataNKawaguchiYWellerSKSatoY 2007 Enhanced phosphorylation of transcription factor sp1 in response to herpes simplex virus type 1 infection is dependent on the ataxia telangiectasia-mutated protein. J Virol 81 9653 9664
57. KimDBDeLucaNA 2002 Phosphorylation of transcription factor Sp1 during herpes simplex virus type 1 infection. J Virol 76 6473 6479
58. ImbalzanoAAShepardAADeLucaNA 1990 Functional relevance of specific interactions between herpes simplex virus type 1 ICP4 and sequences from the promoter-regulatory domain of the viral thymidine kinase gene. J Virol 64 2620 2631
59. QiuYHoareau-AveillaCOlteanSHarperSJBatesDO 2009 The anti-angiogenic isoforms of VEGF in health and disease. Biochem Soc Trans 37 1210 1213
60. SmithRWMalikPClementsJB 2005 The herpes simplex virus ICP27 protein: a multifunctional post-transcriptional regulator of gene expression. Biochem Soc Trans 33 499 501
61. IssaALeTXShoushtariANShieldsJDSwartzMA 2009 Vascular endothelial growth factor-C and C-C chemokine receptor 7 in tumor cell-lymphatic cross-talk promote invasive phenotype. Cancer Res 69 349 357
62. NishimotoFSakataMMinekawaROkamotoYMiyakeA 2009 Metal transcription factor-1 is involved in hypoxia-dependent regulation of placenta growth factor in trophoblast-derived cells. Endocrinology 150 1801 1808
63. WuestTFarberJLusterACarrDJ 2006 CD4+ T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection. Cell Immunol 243 83 89
64. WuestTRCarrDJ 2008 Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the antiviral response to herpes simplex virus 1 infection. J Immunol 181 7985 7993
65. FukumuraDXavierRSugiuraTChenYParkEC 1998 Tumor induction of VEGF promoter activity in stromal cells. Cell 94 715 725
66. GerberHPHillanKJRyanAMKowalskiJKellerGA 1999 VEGF is required for growth and survival in neonatal mice. Development 126 1149 1159
67. DeLucaNASchafferPA 1987 Activities of herpes simplex virus type 1 ICP4 genes specifying nonsense peptides. Nucleic Acids Res 15 4491 4511
68. HalfordWPKempCDIslerJADavidoDJSchafferPA 2001 ICP0, ICP4, or VP16 expressed from adenovirus vectors induces reactivation of latent herpes simplex virus type 1 in primary cultures of latently infected trigeminal ganglion cells. J Virol 75 6144 6153
69. ProençaJTColemanHMConnorVWintonDJEfstathiouS 2008 A historical analysis of herpes simplex virus promoter activation in vivo reveals distinct populations of latently infected neurons. J Gen Virol 89 2965 2974
70. Von MarschallZCramerTHöckerMFinkenzellerGWiedenmannB 2001 Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma. Gut 48 87 96
71. HärlePCullVAgbagaMPSilvermanRWilliamsBR 2002 Differential effect of murine alpha/beta interferon transgenes on antagonization of herpes simplex virus type 1 replication. J Virol 76 6558 6567
72. BeasleyNJPrevoRBanerjiSLeekRDMooreJ 2002 Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res 62 1315 1320
73. FunakiHNishimuraGHaradaSNinomiyaITeradaI 2003 Expression of vascular endothelial growth factor D is associated with lymph node metastasis in human colorectal carcinoma. Oncology 64 416 422
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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