Epstein-Barr Virus Large Tegument Protein BPLF1 Contributes to Innate Immune Evasion through Interference with Toll-Like Receptor Signaling

PLoS Pathogens

Volumn 10, Issue 2, 2014, Pages

  van Gent, Michiel ^a   Braem, Steven G E ^a   de Jong, Annemieke ^b   Delagic, Nezira ^c   Peeters, Janneke G C ^a   Boer, Ingrid G J ^a   Moynagh, Paul N ^c   Kremmer, Elisabeth ^d   Wiertz, Emmanuel J ^a   Ovaa, Huib ^b   Griffin, Bryan D ^a   Ressing, Maaike E ^a,e  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b NETHERLANDS CANCER INSTITUTE   (Netherlands)

^c NATIONAL UNIVERSITY OF IRELAND   (Ireland)

^d INSTITUTE OF EPIDEMIOLOGY   (Germany)

^e LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

DEUBIQUITINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 8; LIGASE; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 9; BPLF1 PROTEIN, EPSTEIN BARR VIRUS; BPLF1 PROTEIN, EPSTEIN-BARR VIRUS; VIRUS PROTEIN;

ARTICLE; CONFOCAL MICROSCOPY; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; EPSTEIN BARR VIRUS; FLOW CYTOMETRY; GENE EXPRESSION; GENETIC TRANSFECTION; HUMAN CELL; IMMUNE EVASION; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; IMMUNOPRECIPITATION; INNATE IMMUNITY; LUCIFERASE ASSAY; NONHUMAN; RAT; SIGNAL TRANSDUCTION; TRANSIENT TRANSFECTION; UBIQUITINATION; VIRUS INFECTION; EPSTEIN BARR VIRUS INFECTION; FLUORESCENT ANTIBODY TECHNIQUE; HUMAN; IMMUNOLOGY; METABOLISM;

ENZYME-LINKED IMMUNOSORBENT ASSAY; EPSTEIN-BARR VIRUS INFECTIONS; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HERPESVIRUS 4, HUMAN; HUMANS; IMMUNE EVASION; IMMUNITY, INNATE; IMMUNOBLOTTING; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS; TRANSFECTION; VIRAL REGULATORY AND ACCESSORY PROTEINS;

EID: 84895733835     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003960     Document Type: Article

References (73)

1. Rickinson AB, Kieff E (2007) Epstein-Barr Virus. In: Knipe DM, Howley PM, editors. Field's Virology. Philadelphia: Lippincott Williams & Wilkins. pp. 2655-2700.
2. Kutok JL, Wang F, (2006) Spectrum of Epstein-Barr Virus-Associated Diseases. Annu Rev Pathol Mech Dis 1: 375-404.
3. Iwasaki A, Medzhitov R, (2010) Regulation of Adaptive Immunity by the Innate Immune System. Science 327: 291-295.
4. Szomolanyi-Tsuda E, Liang X, Welsh RM, Kurt-Jones EA, Finberg RW, (2006) Role for TLR2 in NK Cell-Mediated Control of Murine Cytomegalovirus In Vivo. Journal of Virology 80: 4286-4291.
5. Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, et al. (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proceedings of the National Academy of Sciences of the United States of America 101: 3516-3521.
6. Zucchini N, Bessou G, Traub S, Robbins SH, Uematsu S, et al. (2008) Cutting Edge: Overlapping Functions of TLR7 and TLR9 for Innate Defense against a Herpesvirus Infection. The Journal of Immunology 180: 5799-5803.
7. Davey GM, Wojtasiak M, Proietto AI, Carbone FR, Heath WR, et al. (2010) Cutting Edge: Priming of CD8 T Cell Immunity to Herpes Simplex Virus Type 1 Requires Cognate TLR3 Expression In Vivo. The Journal of Immunology 184: 2243-2246.
8. Sorensen LN, Reinert LS, Malmgaard L, Bartholdy C, Thomsen AR, et al. (2008) TLR2 and TLR9 Synergistically Control Herpes Simplex Virus Infection in the Brain. The Journal of Immunology 181: 8604-8612.
9. Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, et al. (2006) Herpes Simplex Virus Encephalitis in Human UNC-93B Deficiency. Science 314: 308-312.
10. Guo Y, Audry M, Ciancanelli M, Alsina L, Azevedo J, et al. (2011) Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. The Journal of Experimental Medicine 208: 2083-2098.
11. Perez de Diego R, Sancho-Shimizu V, Lorenzo L, Puel A, Plancoulaine S, et al. (2010) Human TRAF3 Adaptor Molecule Deficiency Leads to Impaired Toll-like Receptor 3 Response and Susceptibility to Herpes Simplex Encephalitis. Immunity 33: 400-411.
12. Sancho-Shimizu V, rez de Diego R, Lorenzo L, Halwani R, Alangari A, et al. (2011) Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J Clin Invest 121: 4889-4902.
13. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, et al. (2007) TLR3 Deficiency in Patients with Herpes Simplex Encephalitis. Science 317: 1522-1527.
14. Paludan SR, Bowie AG, Horan KA, Fitzgerald KA, (2011) Recognition of herpesviruses by the innate immune system. Nat Rev Immunol 11: 143-154.
15. Ariza ME, Glaser R, Kaumaya PTP, Jones C, Williams MV, (2009) The EBV-Encoded dUTPase Activates NF-kB through the TLR2 and MyD88-Dependent Signaling Pathway. The Journal of Immunology 182: 851-859.
16. Gaudreault E, Fiola S, Olivier M, Gosselin J, (2007) Epstein-Barr Virus Induces MCP-1 Secretion by Human Monocytes via TLR2. J Virol 81: 8016-8024.
17. Fiola S, Gosselin D, Takada K, Gosselin J, (2010) TLR9 Contributes to the Recognition of EBV by Primary Monocytes and Plasmacytoid Dendritic Cells. The Journal of Immunology 185: 3620-3631.
18. Iwakiri D, Zhou L, Samanta M, Matsumoto M, Ebihara T, et al. (2009) Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from Toll-like receptor 3. The Journal of Experimental Medicine 206: 2091-2099.
19. Lim WH, Kireta S, Russ GR, Coates PTH, (2007) Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice. Blood 109: 1043-1050.
20. Quan TE, Roman RM, Rudenga BJ, Holers VM, Craft JE, (2010) Epstein-Barr virus promotes interferon-alpha production by plasmacytoid dendritic cells. Arthritis & Rheumatism 62: 1693-1701.
21. Mogensen TH, (2009) Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clinical Microbiology Reviews 22: 240-273.
22. Takeuchi O, Akira S, (2009) Innate immunity to virus infection. Immunological Reviews 227: 75-86.
23. van Gent M, Griffin BD, Berkhoff EG, van Leeuwen D, Boer IGJ, et al. (2011) EBV Lytic-Phase Protein BGLF5 Contributes to TLR9 Downregulation during Productive Infection. The Journal of Immunology 186: 1694-1702.
24. Wertz IE, Dixit VM, (2010) Signaling to NF-kB: Regulation by Ubiquitination. Cold Spring Harbor Perspectives in Biology 2: 1-19.
25. Boone DL, Turer EE, Lee EG, Ahmad RC, Wheeler MT, et al. (2004) The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol 5: 1052-1060.
26. Brummelkamp TR, Nijman SMB, Dirac AMG, Bernards R, (2003) Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-[kappa]B. Nature 424: 797-801.
27. Isaacson MK, Ploegh HL, (2009) Ubiquitination, Ubiquitin-like Modifiers, and Deubiquitination in Viral Infection. Cell Host Microbe 5: 559-570.
28. Randow F, Lehner PJ, (2009) Viral avoidance and exploitation of the ubiquitin system. Nat Cell Biol 11: 527-534.
29. Gredmark S, Schlieker C, Quesada V, Spooner E, Ploegh HL, (2007) A Functional Ubiquitin-Specific Protease Embedded in the Large Tegument Protein (ORF64) of Murine Gammaherpesvirus 68 Is Active during the Course of Infection. Journal of Virology 81: 10300-10309.
30. Kattenhorn LM, Korbel GA, Kessler BM, Spooner E, Ploegh HL, (2005) A Deubiquitinating Enzyme Encoded by HSV-1 Belongs to a Family of Cysteine Proteases that Is Conserved across the Family Herpesviridae. Mol Cell 19: 547-557.
31. Schlieker C, Korbel GA, Kattenhorn LM, Ploegh HL, (2005) A Deubiquitinating Activity Is Conserved in the Large Tegument Protein of the Herpesviridae. Journal of Virology 79: 15582-15585.
32. Sompallae R, Gastaldello S, Hildebrand S, Zinin N, Hassink G, et al. (2008) Epstein-Barr Virus Encodes Three Bona Fide Ubiquitin-Specific Proteases. Journal of Virology 82: 10477-10486.
33. Ressing ME, Keating SE, van Leeuwen D, Koppers-Lalic D, Pappworth IY, et al. (2005) Impaired Transporter Associated with Antigen Processing-Dependent Peptide Transport during Productive EBV Infection. The Journal of Immunology 174: 6829-6838.
34. Bornkamm GW, Hudewentz J, Freese UK, Zimber U, (1982) Deletion of the Nontransforming Epstein-Barr Virus Strain P3HR-1 Causes Fusion of the Large Internal Repeat to the DSL Region. Journal of Virology 43: 952-968.
35. Kurt-Jones EA, Mandell L, Whitney C, Padgett A, Gosselin K, et al. (2002) Role of Toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils. Blood 100: 1860-1868.
36. de Jong A, Merkx R, Berlin I, Rodenko B, Wijdeven RHM, et al. (2012) Ubiquitin-Based Probes Prepared by Total Synthesis To Profile the Activity of Deubiquitinating Enzymes. ChemBioChem 13: 2251-2258.
37. Tsai CH, Liu MT, Chen MR, Lu J, Yang HL, et al. (1997) Characterization of Monoclonal Antibodies to the Zta and DNase proteins of Epstein-Barr Virus. J Biomed Sci 4: 69-77.
38. Gastaldello S, Hildebrand S, Faridani O, Callegari S, Palmkvist M, et al. (2010) A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases. Nat Cell Biol 12: 351-361.
39. Gastaldello S, Callegari S, Coppotelli G, Hildebrand S, Song M, et al. (2012) Herpes virus deneddylases interrupt the cullin-RING ligase neddylation cycle by inhibiting the binding of CAND1. Journal of Molecular Cell Biology 4: 242-251.
40. Whitehurst CB, Ning S, Bentz GL, Dufour F, Gershburg E, et al. (2009) The Epstein-Barr Virus (EBV) Deubiquitinating Enzyme BPLF1 Reduces EBV Ribonucleotide Reductase Activity. Journal of Virology 83: 4345-4353.
41. Whitehurst CB, Vaziri C, Shackelford J, Pagano JS, (2012) Epstein-Barr Virus BPLF1 Deubiquitinates PCNA and Attenuates Polymerase eta Recruitment to DNA Damage Sites. Journal of Virology 86: 8097-8106.
42. Gastaldello S, Chen X, Callegari S, Masucci MG, (2013) Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells. PLoS Pathog 9: e1003664.
43. Sachdev S, Hoffmann A, Hannink M, (1998) Nuclear Localization of IkBa Is Mediated by the Second Ankyrin Repeat: the IkBa Ankyrin Repeats Define a Novel Class of cis-Acting Nuclear Import Sequences. Molecular and Cellular Biology 18: 2524-2534.
44. Schmaus S, Wolf H, Schwarzmann F, (2004) The Reading Frame BPLF1 of Epstein-Barr Virus: A Homologue of Herpes Simplex Virus Protein VP16. Virus Genes 29: 267-277.
45. Rowe M, Glaunsinger B, van Leeuwen D, Zuo J, Sweetman D, et al. (2007) Host shutoff during productive Epstein-Barr virus infection is mediated by BGLF5 and may contribute to immune evasion. Proceedings of the National Academy of Sciences 104: 3366-3371.
46. Schlieker C, Weihofen WA, Frijns E, Kattenhorn LM, Gaudet R, et al. (2007) Structure of a Herpesvirus-Encoded Cysteine Protease Reveals a Unique Class of Deubiquitinating Enzymes. Mol Cell 25: 677-687.
47. Kim ET, Oh SE, Lee YO, Gibson W, Ahn JH, (2009) Cleavage Specificity of the UL48 Deubiquitinating Protease Activity of Human Cytomegalovirus and the Growth of an Active-Site Mutant Virus in Cultured Cells. Journal of Virology 83: 12046-12056.
48. Roberts APE, Abaitua F, O'Hare P, McNab D, Rixon FJ, et al. (2009) Differing Roles of Inner Tegument Proteins pUL36 and pUL37 during Entry of Herpes Simplex Virus Type 1. Journal of Virology 83: 105-116.
49. Gredmark R, Isaacson MK, Kattenhorn L, Cheung EJ, Watson N, et al. (2009) A Gammaherpesvirus Ubiquitin-Specific Protease Is Involved in the Establishment of Murine Gammaherpesvirus 68 Infection. Journal of Virology 83: 10644-10652.
50. Saito S, Murata T, Kanda T, Isomura H, Narita Y, et al. (2013) Epstein-Barr Virus Deubiquitinase Downregulates TRAF6-Mediated NF-kB Signaling during Productive Replication. Journal of Virology 87: 4060-4070.
51. Ernst R, Claessen JHL, Mueller B, Sanyal S, Spooner E, et al. (2011) Enzymatic Blockade of the Ubiquitin-Proteasome Pathway. PLoS Biol 8: e1000605.
52. Ovaa H, Kessler BM, Rolén U, Galardy PJ, Ploegh HL, et al. (2004) Activity-based ubiquitin-specific protease (USP) profiling of virus-infected and malignant human cells. Proceedings of the National Academy of Sciences of the United States of America 101: 2253-2258.
53. Johannsen E, Luftig M, Chase MR, Weicksel S, Cahir-McFarland E, et al. (2004) Proteins of purified Epstein-Barr virus. Proceedings of the National Academy of Sciences of the United States of America 101: 16286-16291.
54. Abaitua F, Hollinshead M, Bolstad M, Crump CM, O'Hare P, (2012) A Nuclear Localization Signal in Herpesvirus Protein VP1-2 Is Essential for Infection via Capsid Routing to the Nuclear Pore. Journal of Virology 86: 8998-9014.
55. Jovasevic V, Liang L, Roizman B, (2008) Proteolytic Cleavage of VP1-2 Is Required for Release of Herpes Simplex Virus 1 DNA into the Nucleus. Journal of Virology 82: 3311-3319.
56. Schipke J, Pohlmann A, Diestel R, Binz A, Rudolph K, et al. (2012) The C Terminus of the Large Tegument Protein pUL36 Contains Multiple Capsid Binding Sites That Function Differently during Assembly and Cell Entry of Herpes Simplex Virus. Journal of Virology 86: 3682-3700.
57. Wang J, Loveland AN, Kattenhorn LM, Ploegh HL, Gibson W, (2006) High-Molecular-Weight Protein (pUL48) of Human Cytomegalovirus Is a Competent Deubiquitinating Protease: Mutant Viruses Altered in Its Active-Site Cysteine or Histidine Are Viable. Journal of Virology 80: 6003-6012.
58. Vazirabadi G, Geiger TR, Coffin III, Martin JM, (2003) Epstein-Barr virus latent membrane protein-1 (LMP-1) and lytic LMP-1 localization in plasma membrane-derived extracellular vesicles and intracellular virions. Journal of General Virology 84: 1997-2008.
59. Pandya J, Walling DM, (2006) Oncogenic Activity of Epstein-Barr Virus Latent Membrane Protein 1 (LMP-1) Is Down-Regulated by Lytic LMP-1. Journal of Virology 80: 8038-8046.
60. Erickson KD, Martin JM, (2000) The Late Lytic LMP-1 Protein of Epstein-Barr Virus Can Negatively Regulate LMP-1 Signaling. Journal of Virology 74: 1057-1060.
61. Mansur DS, Maluquer de Motes C, Unterholzner L, Sumner RP, Ferguson BJ, et al. (2013) Poxvirus Targeting of E3 Ligase ßTrCP by Molecular Mimicry: A Mechanism to Inhibit NF-kB Activation and Promote Immune Evasion and Virulence. PLoS Pathog 9: e1003183.
62. Yu Y, Wang SE, Hayward GS, (2005) The KSHV Immediate-Early Transcription Factor RTA Encodes Ubiquitin E3 Ligase Activity that Targets IRF7 for Proteosome-Mediated Degradation. Immunity 22: 59-70.
63. Karim R, Tummers B, Meyers C, Biryukov JL, Alam S, et al. (2013) Human Papillomavirus (HPV) Upregulates the Cellular Deubiquitinase UCHL1 to Suppress the Keratinocyte's Innate Immune Response. PLoS Pathog 9: e1003384.
64. Daubeuf S, Singh D, Tan Y, Liu H, Federoff HJ, et al. (2009) HSV ICP0 recruits USP7 to modulate TLR-mediated innate response. Blood 113: 3264-3275.
65. van Kasteren PB, Beugeling C, Ninaber DK, Frias-Staheli N, van Boheemen S, et al. (2012) Arterivirus and Nairovirus Ovarian Tumor Domain-Containing Deubiquitinases Target Activated RIG-I To Control Innate Immune Signaling. Journal of Virology 86: 773-785.
66. van Kasteren PB, Bailey-Elkin BA, James TW, Ninaber DK, Beugeling C, et al. (2013) Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells. Proceedings of the National Academy of Sciences 110: E838-E847.
67. Balakirev MY, Jaquinod M, Haas AL, Chroboczek J, (2002) Deubiquitinating Function of Adenovirus Proteinase. Journal of Virology 76: 6323-6331.
68. Inn KS, Lee SH, Rathbun JY, Wong LY, Toth Z, et al. (2011) Inhibition of RIG-I mediated signaling by Kaposi's sarcoma-associated herpesvirus-encoded deubiquitinase ORF64. Journal of Virology 85: 10899-10904.
69. Ressing ME, Wiertz EJHJ, (2008) Manipulation of the immune response by Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus: Consequences for tumor development. Seminars in Cancer Biology 18: 379-380.
70. Mohamed MR, McFadden G, (2009) NF-kB inhibitors: Strategies from poxviruses. Cell Cycle 8: 3125-3132.
71. Wu L, Fossum E, Joo CH, Inn KS, Shin YC, et al. (2009) Epstein-Barr Virus LF2: an Antagonist to Type I Interferon. Journal of Virology 83: 1140-1146.
72. Hahn AM, Huye LE, Ning S, Webster-Cyriaque J, Pagano JS, (2005) Interferon Regulatory Factor 7 Is Negatively Regulated by the Epstein-Barr Virus Immediate-Early Gene, BZLF-1. Journal of Virology 79: 10040-10052.
73. Wang JT, Doong SL, Teng SC, Lee CP, Tsai CH, et al. (2009) Epstein-Barr Virus BGLF4 Kinase Suppresses the Interferon Regulatory Factor 3 Signaling Pathway. Journal of Virology 83: 1856-1869.