Molecular mechanisms deployed by virally encoded g protein-coupled receptors in human diseases

Annual Review of Pharmacology and Toxicology

Volumn 53, Issue , 2013, Pages 331-354

  Montaner, Silvia ^a   Kufareva, Irina ^b   Abagyan, Ruben ^b   Silvio Gutkind, J ^c  

^a UNIVERSITY OF MARYLAND   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

chemokine receptors; constitutive activity; human viruses; signal transduction; structure; virus associated malignancies

Indexed keywords

BETA ARRESTIN; CHEMOKINE; CHEMOKINE RECEPTOR; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; VIRUS PROTEIN;

EPSTEIN BARR VIRUS; HERPES VIRUS; HUMAN CYTOMEGALOVIRUS; HUMAN HERPESVIRUS 6; HUMAN HERPESVIRUS 7; KAPOSI SARCOMA; MOLECULAR MODEL; NONHUMAN; PHYLOGENY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; VIRUS CARCINOGENESIS; VIRUS ONCOGENE; VIRUS PATHOGENESIS;

ANIMALS; GENOME, VIRAL; HERPESVIRIDAE; HUMANS; RECEPTORS, G-PROTEIN-COUPLED; VIRAL PROTEINS;

HERPESVIRIDAE; MAMMALIA;

EID: 84872238380     PISSN: 03621642     EISSN: 15454304     Source Type: Book Series    
DOI: 10.1146/annurev-pharmtox-010510-100608     Document Type: Review

References (134)

1. Pierce KL, Premont RT, Lefkowitz RJ. 2002. Seven-transmembrane receptors. Nat. Rev. Mol. Cell Biol. 3:639-50
2. Flower DR. 1999. Modelling G-protein-coupled receptors for drug design. Biochim. Biophys. Acta 1422:207-34
3. Cabrera-Vera TM, Vanhauwe J, Thomas TO, Medkova M, Preininger A, et al. 2003. Insights into G protein structure, function, and regulation. Endocr. Rev. 24:765-81
4. Sodhi A, Montaner S, Gutkind JS. 2004. Viral hijacking of G-protein-coupled-receptor signalling networks. Nat. Rev. Mol. Cell Biol. 5:998-1012
5. Barton E, Mandal P, Speck SH. 2011. Pathogenesis and host control of gammaherpesviruses: lessons from the mouse. Annu. Rev. Immunol. 29:351-97
6. Sherrill JD, Stropes MP, Schneider OD, Koch DE,Bittencourt FM, et al. 2009. Activation of intracellular signaling pathways by the murine cytomegalovirus G protein-coupled receptor M33 occurs via PLC-β/PKC- dependent and-independent mechanisms. J. Virol. 83:8141-52
7. Wu B, Chien EY, Mol CD, Fenalti G, Liu W, et al. 2010. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330:1066-71
8. Kufareva I, Rueda M, Katritch V, Stevens RC, Abagyan R. 2011. Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment. Structure 19:1108-26
9. Jenner RG, Boshoff C. 2002. The molecular pathology of Kaposi's sarcoma-associated herpesvirus. Biochim. Biophys. Acta 1602:1-22
10. Mesri EA, Cesarman E, Boshoff C. 2010. Kaposi's sarcoma and its associated herpesvirus. Nat. Rev. Cancer 10:707-19
11. Ganem D. 1998. Human herpesvirus 8 and its role in the genesis of Kaposi's sarcoma. Curr. Clin. Top. Infect. Dis. 18:237-51
12. Dourmishev LA, Dourmishev AL, Palmeri D, Schwartz RA, Lukac DM. 2003. Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis. Microbiol. Mol. Biol. Rev. 67:175-212
13. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, et al. 1994. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865-69
14. Moore PS, Chang Y. 2001. Molecular virology of Kaposi's sarcoma-associated herpesvirus. Philos. Trans. R. Soc. Lond. B 356:499-516
15. Cesarman E. 2002. The role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. Recent Results Cancer Res. 159:27-37
16. Ganem D. 2007. KSHV-induced oncogenesis. In Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis, ed. A Arvin, G Campadelli-Fiume, E Mocarski, PS Moore, B Roizman, et al., chap. 56. Cambridge, UK: Cambridge Univ. Press
17. Bais C, Santomasso B, Coso O, Arvanitakis L, Raaka EG, et al. 1998. G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature 391:86-89
18. Arvanitakis L, Geras-Raaka E, Varma A, Gershengorn MC, Cesarman E. 1997. Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature 385:347-50
19. Cesarman E, Nador RG, Bai F, Bohenzky RA, Russo JJ, et al. 1996. Kaposi's sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi's sarcoma and malignant lymphoma. J. Virol. 70:8218-23
20. Abagyan RA, Totrov MM, Kuznetsov DA. 1994. ICM-a new method for protein modeling and design: applications to docking and structure prediction from the distorted native conformation. J. Comput. Chem. 15:488-506
21. AbagyanR,Batalov S,CardozoT,TotrovM,Webber J,Zhou Y. 1997. Homology modelingwith internal coordinate mechanics: deformation zone mapping and improvements of models via conformational search. Proteins Suppl. 1:29-37
22. Ballesteros JA, Weinstein H. 1995. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods Neurosci. 25:366-428
23. Porter JE, Hwa J, Perez DM. 1996. Activation of the α1b-adrenergic receptor is initiated by disruption of an interhelical salt bridge constraint. J. Biol. Chem. 271:28318-23
24. Ho HH, Ganeshalingam N, Rosenhouse-Dantsker A, Osman R, Gershengorn MC. 2001. Charged residues at the intracellular boundary of transmembrane helices 2 and 3 independently affect constitutive activity of Kaposi's sarcoma-associated herpesvirusGprotein-coupled receptor. J. Biol. Chem. 276:1376-82
25. Verzijl D, Pardo L, vanDijkM,Gruijthuijsen YK, Jongejan A, et al. 2006. Helix 8 of the viral chemokine receptor ORF74 directs chemokine binding. J. Biol. Chem. 281:35327-35
26. Liu C, Sandford G, Fei G, Nicholas J. 2004. Gα protein selectivity determinant specified by a viral chemokine receptor-conserved region in the C tail of the human herpesvirus 8 G protein-coupled receptor. J. Virol. 78:2460-71
27. Rosenkilde MM, Kledal TN, Holst PJ, Schwartz TW. 2000. Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74. J. Biol. Chem. 275:26309-15
28. Rosenkilde MM, Schwartz TW. 2000. Potency of ligands correlates with affinity measured against agonist and inverse agonists but not against neutral ligand in constitutively active chemokine receptor. Mol. Pharmacol. 57:602-9
29. Feng H, Sun Z, Farzan MR, Feng P. 2010. Sulfotyrosines of the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promote tumorigenesis through autocrine activation. J. Virol. 84:3351-61
30. Gershengorn MC, Geras-Raaka E, Varma A, Clark-Lewis I. 1998. Chemokines activate Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor in mammalian cells in culture. J. Clin. Investig. 102:1469-72
31. Rosenkilde MM, Waldhoer M, Luttichau HR, Schwartz TW. 2001. Virally encoded 7TM receptors. Oncogene 20:1582-93
32. SodhiA,Montaner S,Gutkind JS. 2004. Does dysregulation of a deregulated viralGPCRtriggerKaposi's sarcomagenesis? FASEB J. 18:422-27
33. Montaner S, Sodhi A,Molinolo A, Bugge TH, Sawai ET, et al. 2003. Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3:23-36
34. Guo HG, SadowskaM,ReidW,Tschachler E,Hayward G, Reitz M. 2003. Kaposi's sarcoma-like tumors in a human herpesvirus 8 ORF74 transgenic mouse. J. Virol. 77:2631-39
35. Yang TY, Chen SC, Leach MW, Manfra D, Homey B, et al. 2000. Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma. J. Exp. Med. 191:445-54
36. Jensen KK, Manfra DJ, Grisotto MG, Martin AP, Vassileva G, et al. 2005. The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi's sarcoma. J. Immunol. 174:3686-94
37. Mutlu AD, Cavallin LE, Vincent L, Chiozzini C, Eroles P, et al. 2007. In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: a cell and animal model of virally induced Kaposi's sarcoma. Cancer Cell 11:245-58
38. Montaner S, Sodhi A, Pece S,Mesri EA,Gutkind JS. 2001. The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B. Cancer Res. 61:2641-48
39. Bais C, Van Geelen A, Eroles P, Mutlu A, Chiozzini C, et al. 2003. Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/KDR. Cancer Cell 3:131-43
40. Sodhi A, Montaner S, Patel V, Gomez-Roman J, Li Y, et al. 2004. Akt plays a central role in sarcomagenesis induced by Kaposi's sarcoma herpesvirus-encoded G protein-coupled receptor. Proc. Natl. Acad. Sci. USA 101:4821-26
41. Sodhi A, Chaisuparat R, Hu J, Ramsdell AK, Manning BD, et al. 2006. The TSC2/mTOR pathway drives endothelial cell transformation induced by theKaposi's sarcoma-associated herpesvirusGproteincoupled receptor. Cancer Cell 10:133-43
42. Jham BC, Ma T, Hu J, Chaisuparat R, Friedman ER, et al. 2011. Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma. PLoS ONE 6:e19103
43. Ma T, Jham BC,Hu J, Friedman ER, Basile JR, et al. 2010. ViralGprotein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma. Proc. Natl. Acad. Sci. USA 107:14363-68
44. Hu J, Jham BC, Ma T, Friedman ER, Ferreira L, et al. 2011. Angiopoietin-like 4: a novel molecular hallmark in oral Kaposi's sarcoma. Oral Oncol. 47:371-75
45. Campistol JM, Gutierrez-Dalmau A, Torregrosa JV. 2004. Conversion to sirolimus: a successful treatment for posttransplantation Kaposi's sarcoma. Transplantation 77:760-62
46. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, et al. 2005. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N. Engl. J. Med. 352:1317-23
47. Chaisuparat R, Hu J, Jham BC, Knight ZA, Shokat KM, Montaner S. 2008. Dual inhibition of PI3Kα and mTOR as an alternative treatment for Kaposi's sarcoma. Cancer Res. 68:8361-68
48. Montaner S. 2007. Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor: emerging insights into the molecular oncogenesis and treatment of Kaposi's sarcoma. Cell Cycle 6:438-43
49. Martin D, Galisteo R,Molinolo AA, Wetzker R, Hirsch E, Gutkind JS. 2011. PI3Kγmediates Kaposi's sarcoma-associated herpesvirus vGPCR-induced sarcomagenesis. Cancer Cell 19:805-13
50. Sodhi A,Montaner S, Patel V, Zohar M, Bais C, et al. 2000. TheKaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1α. Cancer Res. 60:4873-80
51. Montaner S, Sodhi A, Servitja JM, Ramsdell AK, Barac A, et al. 2004. The small GTPase Rac1 links the Kaposi sarcoma-associated herpesvirus vGPCR to cytokine secretion and paracrine neoplasia. Blood 104:2903-11
52. Couty JP, Geras-Raaka E, Weksler BB, Gershengorn MC. 2001. Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor signals through multiple pathways in endothelial cells. J. Biol. Chem. 276:33805-11
53. Pati S, Cavrois M, Guo HG, Foulke JS Jr., Kim J, et al. 2001. Activation of NF-κB by the human herpesvirus 8 chemokine receptor ORF74: evidence for a paracrinemodel ofKaposi's sarcoma pathogenesis. J. Virol. 75:8660-73
54. Schwarz M, Murphy PM. 2001. Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor constitutively activates NF-κB and induces proinflammatory cytokine and chemokine production via a C-terminal signaling determinant. J. Immunol. 167:505-13
55. Martin D, Galisteo R, Ji Y, Montaner S, Gutkind JS. 2008. An NF-κB gene expression signature contributes to Kaposi's sarcoma virus vGPCR-induced direct and paracrine neoplasia. Oncogene 27:1844-52
56. Ma Q, Cavallin LE, Yan B, Zhu S, Duran EM, et al. 2009. Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma. Proc. Natl. Acad. Sci. USA 106:8683-88
57. Tan W, Palmby TR, Gavard J, Amornphimoltham P, Zheng Y, Gutkind JS. 2008. An essential role for Rac1 in endothelial cell function and vascular development. FASEB J. 22:1829-38
58. Polson AG, Wang D, DeRisi J, Ganem D. 2002. Modulation of host gene expression by the constitutively active G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus. Cancer Res. 62:4525-30
59. Cannon M, Philpott NJ, Cesarman E. 2003. The Kaposi's sarcoma-associated herpesvirus G proteincoupled receptor has broad signaling effects in primary effusion lymphoma cells. J. Virol. 77:57-67
60. Cannon ML, Cesarman E. 2004. The KSHV G protein-coupled receptor signals via multiple pathways to induce transcription factor activation in primary effusion lymphoma cells. Oncogene 23:514-23
61. Pati S, Foulke JS Jr, Barabitskaya O, Kim J, Nair BC, et al. 2003. Human herpesvirus 8-encoded vGPCR activates nuclear factor of activated T cells and collaborates with human immunodeficiency virus type 1 Tat. J. Virol. 77:5759-73
62. Schulz TF. 2001. KSHV/HHV8-associated lymphoproliferations in the AIDS setting. Eur. J. Cancer 37:1217-26
63. Hideshima T, Chauhan D, Teoh G, Raje N, Treon SP, et al. 2000. Characterization of signaling cascades triggered by human interleukin-6 versus Kaposi's sarcoma-associated herpes virus-encoded viral interleukin 6. Clin. Cancer Res. 6:1180-89
64. Goodrum F, Caviness K, Zagallo P. 2012. Human cytomegalovirus persistence. Cell. Microbiol. 14:644-55
65. Revello MG, Gerna G. 2004. Pathogenesis and prenatal diagnosis of human cytomegalovirus infection. J. Clin. Virol. 29:71-83
66. Cobbs CS. 2011. Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis. Herpesviridae 2:10
67. Streblow DN,Orloff SL, Nelson JA. 2001. Do pathogens accelerate atherosclerosis? J. Nutr. 131:2798S-804S
68. Chee MS, Satchwell SC, Preddie E, Weston KM, Barrell BG. 1990. Human cytomegalovirus encodes three G protein-coupled receptor homologues. Nature 344:774-77
69. Gao JL, Murphy PM. 1994. Human cytomegalovirus open reading frame US28 encodes a functional β chemokine receptor. J. Biol. Chem. 269:28539-42
70. Kuhn DE, Beall CJ, Kolattukudy PE. 1995. The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity. Biochem. Biophys. Res. Commun. 211:325-30
71. Casarosa P, Menge WM, Minisini R, Otto C, van Heteren J, et al. 2003. Identification of the first nonpeptidergic inverse agonist for a constitutively active viral-encoded G protein-coupled receptor. J. Biol. Chem. 278:5172-78
72. Hulshof JW, Vischer HF, Verheij MH, Fratantoni SA, Smit MJ, et al. 2006. Synthesis and pharmacological characterization of novel inverse agonists acting on the viral-encoded chemokine receptor US28. Bioorg. Med. Chem. 14:7213-30
73. Vischer HF, Hulshof JW, Hulscher S, Fratantoni SA, Verheij MH, et al. 2010. Identification of novel allosteric nonpeptidergic inhibitors of the human cytomegalovirus-encoded chemokine receptor US28. Bioorg. Med. Chem. 18:675-88
74. Bond RA, Ijzerman AP. 2006. Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery. Trends Pharmacol. Sci. 27:92-96
75. Smit MJ, Vischer HF, Bakker RA, Jongejan A, Timmerman H, et al. 2007. Pharmacogenomic and structural analysis of constitutive G protein-coupled receptor activity. Annu. Rev. Pharmacol. Toxicol. 47:53-87
76. Zhang WB, Navenot JM, Haribabu B, Tamamura H, Hiramatu K, et al. 2002. A point mutation that confers constitutive activity to CXCR4 reveals that T140 is an inverse agonist and that AMD3100 and ALX40-4C are weak partial agonists. J. Biol. Chem. 277:24515-21
77. Groblewski T,Maigret B, Larguier R, Lombard C, Bonnafous JC,Marie J. 1997. Mutation of Asn111 in the third transmembrane domain of the AT1A angiotensin II receptor induces its constitutive activation. J. Biol. Chem. 272:1822-26
78. Savarese TM,Wang CD, Fraser CM. 1992. Site-directed mutagenesis of the rat m1 muscarinic acetylcholine receptor: role of conserved cysteines in receptor function. J. Biol. Chem. 267:11439-48
79. Casarosa P, Bakker RA, Verzijl D, Navis M, Timmerman H, et al. 2001. Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J. Biol. Chem. 276:1133-37
80. Waldhoer M, Kledal TN, Farrell H, Schwartz TW. 2002. Murine cytomegalovirus (CMV) M33 and human CMV US28 receptors exhibit similar constitutive signaling activities. J. Virol. 76:8161-68
81. Mokros T, Rehm A, Droese J, Oppermann M, Lipp M, Hopken UE. 2002. Surface expression and endocytosis of the human cytomegalovirus-encoded chemokine receptor US28 is regulated by agonistindependent phosphorylation. J. Biol. Chem. 277:45122-28
82. Waldhoer M, Casarosa P, Rosenkilde MM, Smit MJ, Leurs R, et al. 2003. The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis. J. Biol. Chem. 278:19473-82
83. Miller WE, Houtz DA, Nelson CD, Kolattukudy PE, Lefkowitz RJ. 2003. G-protein-coupled receptor (GPCR) kinase phosphorylation and β-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus US28 GPCR. J. Biol. Chem. 278:21663-71
84. Bodaghi B, Jones TR,Zipeto D, Vita C, Sun L, et al. 1998. Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirusinfected cells. J. Exp. Med. 188:855-66
85. Billstrom MA, Johnson GL, Avdi NJ, Worthen GS. 1998. Intracellular signaling by the chemokine receptor US28 during human cytomegalovirus infection. J. Virol. 72:5535-44
86. Randolph-Habecker JR, Rahill B, Torok-Storb B, Vieira J, Kolattukudy PE, et al. 2002. The expression of the cytomegalovirus chemokine receptor homologUS28 sequesters biologically activeCCchemokines and alters IL-8 production. Cytokine 19:37-46
87. McLean KA, Holst PJ, Martini L, Schwartz TW, Rosenkilde MM. 2004. Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74. Virology 325:241-51
88. Moepps B, Tulone C, Kern C, Minisini R, Michels G, et al. 2008. Constitutive serum response factor activation by the viral chemokine receptor homologue pUS28 is differentially regulated by Gαq/11 and Gα16. Cell Signal 20:1528-37
89. Melnychuk RM, Streblow DN, Smith PP, Hirsch AJ, Pancheva D, Nelson JA. 2004. Human cytomegalovirus-encoded G protein-coupled receptor US28 mediates smooth muscle cell migration through Gα12. J. Virol. 78:8382-91
90. Streblow DN, Soderberg-Naucler C, Vieira J, Smith P, Wakabayashi E, et al. 1999. The human cytomegalovirus chemokine receptor US28 mediates vascular smoothmuscle cell migration. Cell 99:511-20
91. StreblowDN,Vomaske J, SmithP,Melnychuk R, Hall L, et al. 2003.Humancytomegalovirus chemokine receptor US28-induced smooth muscle cell migration is mediated by focal adhesion kinase and Src. J. Biol. Chem. 278:50456-65
92. Maussang D, Langemeijer E, Fitzsimons CP, Stigter-van Walsum M, Dijkman R, et al. 2009. The human cytomegalovirus-encoded chemokine receptor US28 promotes angiogenesis and tumor formation via cyclooxygenase-2. Cancer Res. 69:2861-69
93. Maussang D, Verzijl D, van Walsum M, Leurs R, Holl J, et al. 2006. Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis. Proc. Natl. Acad. Sci. USA 103:13068-73
94. Soroceanu L, Matlaf L, Bezrookove V, Harkins L, Martinez R, et al. 2011. Human cytomegalovirus US28 found in glioblastoma promotes an invasive and angiogenic phenotype. Cancer Res. 71:6643-53
95. DziurzynskiK,Wei J, QiaoW,Hatiboglu MA, Kong LY, et al. 2011. Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin. Cancer Res. 17:4642-49
96. Slinger E, Maussang D, Schreiber A, Siderius M, Rahbar A, et al. 2010. HCMV-encoded chemokine receptor US28 mediates proliferative signaling through the IL-6-STAT3 axis. Sci. Signal. 3:ra58
97. Bongers G, Maussang D, Muniz LR, Noriega VM, Fraile-Ramos A, et al. 2010. The cytomegalovirusencoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice. J. Clin. Investig. 120:3969-78
98. Vischer HF, Leurs R, Smit MJ. 2006. HCMV-encoded G-protein-coupled receptors as constitutively active modulators of cellular signaling networks. Trends Pharmacol. Sci. 27:56-63
99. Margulies BJ, Gibson W. 2007. The chemokine receptor homologue encoded by US27 of human cytomegalovirus is heavily glycosylated and is present in infected human foreskin fibroblasts and enveloped virus particles. Virus Res. 123:57-71
100. Stapleton LK, Arnolds KL, Lares AP, Devito TM, Spencer JV. 2012. Receptor chimeras demonstrate that the C-terminal domain of the human cytomegalovirusUS27 gene product is necessary and sufficient for intracellular receptor localization. Virol J. 9:42
101. Tschische P, Tadagaki K, Kamal M, Jockers R, Waldhoer M. 2011. Heteromerization of human cytomegalovirus encoded chemokine receptors. Biochem. Pharmacol. 82:610-19
102. O'Connor CM, Shenk T. 2011. Human cytomegalovirus pUS27Gprotein-coupled receptor homologue is required for efficient spread by the extracellular route but not for direct cell-to-cell spread. J. Virol. 85:3700-7
103. Michel D, Milotic I, Wagner M, Vaida B, Holl J, et al. 2005. The human cytomegalovirus UL78 gene is highly conserved among clinical isolates, but is dispensable for replication in fibroblasts and a renal artery organ-culture system. J. Gen. Virol. 86:297-306
104. Burkitt D, O'Conor GT. 1961. Malignant lymphoma in African children: I. A clinical syndrome. Cancer 14:258-69
105. Epstein MA, Henle G, Achong BG, Barr YM. 1965. Morphological and biological studies on a virus in cultured lymphoblasts from Burkitt's lymphoma. J. Exp. Med. 121:761-70
106. Niedobitek G, Young LS. 1994. Epstein-Barr virus persistence and virus-associated tumours. Lancet 343:333-35
107. Beisser PS, Verzijl D, Gruijthuijsen YK, Beuken E, Smit MJ, et al. 2005. The Epstein-Barr virus BILF1 gene encodes a G protein-coupled receptor that inhibits phosphorylation of RNA-dependent protein kinase. J. Virol. 79:441-49
108. Paulsen SJ, Rosenkilde MM, Eugen-Olsen J, Kledal TN. 2005. Epstein-Barr virus-encoded BILF1 is a constitutively active G protein-coupled receptor. J. Virol. 79:536-46
109. Ressing ME, Horst D, Griffin BD, Tellam J, Zuo J, et al. 2008. Epstein-Barr virus evasion of CD8+ and CD4+ T cell immunity via concerted actions of multiple gene products. Semin. Cancer Biol. 18:397-408
110. Zuo J, Quinn LL, Tamblyn J, Thomas WA, Feederle R, et al. 2011. The Epstein-Barr virus-encoded BILF1 protein modulates immune recognition of endogenously processed antigen by targeting major histocompatibility complex class I molecules trafficking on both the exocytic and endocytic pathways. J. Virol. 85:1604-14
111. Zuo J, Currin A, Griffin BD, Shannon-Lowe C, Thomas WA, et al. 2009. The Epstein-Barr virus G-protein-coupled receptor contributes to immune evasion by targeting MHC class I molecules for degradation. PLoS Pathogens 5:e1000255
112. Vischer HF, Nijmeijer S, Smit MJ, Leurs R. 2008. Viral hijacking of human receptors through heterodimerization. Biochem. Biophys. Res. Commun. 377:93-97
113. Nijmeijer S, Leurs R, Smit MJ, Vischer HF. 2010. The Epstein-Barr virus-encoded G protein-coupled receptor BILF1 hetero-oligomerizes with human CXCR4, scavenges Gαi proteins, and constitutively impairs CXCR4 functioning. J. Biol. Chem. 285:29632-41
114. Lyngaa R, Norregaard K, Kristensen M, Kubale V, Rosenkilde MM, Kledal TN. 2010. Cell transformation mediated by the Epstein-Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling. Oncogene 29:4388-98
115. Birkenbach M, Josefsen K, Yalamanchili R, Lenoir G, Kieff E. 1993. Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors. J. Virol. 67:2209-20
116. Burgstahler R, Kempkes B, Steube K, Lipp M. 1995. Expression of the chemokine receptor BLR2/EBI1 is specifically transactivated by Epstein-Barr virus nuclear antigen 2. Biochem. Biophys. Res. Commun. 215:737-43
117. Nakayama T, Fujisawa R, IzawaD,HieshimaK,Takada K, Yoshie O. 2002. Human B cells immortalized with Epstein-Barr virus upregulate CCR6 and CCR10 and downregulate CXCR4 and CXCR5. J. Virol. 76:3072-77
118. Schwartz TW, Frimurer TM, Holst B, Rosenkilde MM, Elling CE. 2006. Molecular mechanism of 7TM receptor activation-a global toggle switch model. Annu. Rev. Pharmacol. Toxicol. 46:481-519
119. Stein JV, Soriano SF, M'rini C, Nombela-Arrieta C, de Buitrago GG, et al. 2003. CCR7-mediated physiological lymphocyte homing involves activation of a tyrosine kinase pathway. Blood 101:38-44
120. Tilton B, Ho L, Oberlin E, Loetscher P, Baleux F, et al. 2000. Signal transduction by CXC chemokine receptor 4: stromal cell-derived factor 1 stimulates prolonged protein kinase B and extracellular signal-regulated kinase 2 activation in T lymphocytes. J. Exp. Med. 192:313-24
121. Adachi S, Kuwata T, Miyaike M, Iwata M. 2001. Induction of CCR7 expression in thymocytes requires both ERK signal and Ca2+ signal. Biochem. Biophys. Res. Commun. 288:1188-93
122. Bardi G, Niggli V, Loetscher P. 2003. Rho kinase is required for CCR7-mediated polarization and chemotaxis of T lymphocytes. FEBS Lett. 542:79-83
123. Yanagawa Y, Onoe K. 2003. CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities. Blood 101:4923-29
124. Levy JA. 1997. Three new human herpesviruses (HHV6, 7, and 8). Lancet 349:558-63
125. Dockrell DH. 2003. Human herpesvirus 6: molecular biology and clinical features. J. Med. Microbiol. 52:5-18
126. de Pagter PJ, Schuurman R, Visscher H, de Vos M, Bierings M, et al. 2008. Human herpes virus 6 plasma DNA positivity after hematopoietic stem cell transplantation in children: an important risk factor for clinical outcome. Biol. Blood Marrow Transplant. 14:831-39
127. Betts BC, Young JA, Ustun C, Cao Q, Weisdorf DJ. 2011. Human herpesvirus 6 infection after hematopoietic cell transplantation: Is routine surveillance necessary? Biol. Blood Marrow Transplant. 17:1562-68
128. Isegawa Y, Ping Z, Nakano K, Sugimoto N, Yamanishi K. 1998. Human herpesvirus 6 open reading frame U12 encodes a functional β-chemokine receptor. J. Virol. 72:6104-12
129. Nakano K, Tadagaki K, Isegawa Y, Aye MM, Zou P, Yamanishi K. 2003. Human herpesvirus 7 open reading frame U12 encodes a functional β-chemokine receptor. J. Virol. 77:8108-15
130. Tadagaki K, Nakano K, Yamanishi K. 2005. Human herpesvirus 7 open reading frames U12 and U51 encode functional β-chemokine receptors. J. Virol. 79:7068-76
131. Milne RS, Mattick C, Nicholson L, Devaraj P, Alcami A, Gompels UA. 2000. RANTES binding and down-regulation by a novel human herpesvirus-6 βchemokine receptor. J. Immunol. 164:2396-404
132. Catusse J, Spinks J, Mattick C, Dyer A, Laing K, et al. 2008. Immunomodulation by herpesvirus U51A chemokine receptor via CCL5 and FOG-2 down-regulation plus XCR1 and CCR7 mimicry in human leukocytes. Eur. J. Immunol. 38:763-77
133. Fitzsimons CP, Gompels UA, Verzijl D, Vischer HF, Mattick C, et al. 2006. Chemokine-directed trafficking of receptor stimulus to different G proteins: selective inducible and constitutive signaling by human herpesvirus 6-encoded chemokine receptor U51. Mol. Pharmacol. 69:888-98
134. Zhen Z, Bradel-Tretheway B, Sumagin S, Bidlack JM, Dewhurst S. 2005. The human herpesvirus 6 G protein-coupled receptor homolog U51 positively regulates virus replication and enhances cell-cell fusion in vitro. J. Virol. 79:11914-24