Functional analysis of the murine cytomegalovirus chemokine receptor homologue M33: Ablation of constitutive signaling is associated with an attenuated phenotype in vivo

Journal of Virology

Volumn 82, Issue 4, 2008, Pages 1884-1898

  Case, Ruth ^a   Sharp, Emma ^a   Benned Jensen, Tau ^b   Rosenkilde, Mette M ^b   Davis Poynter, Nicholas ^a,c   Farrell, Helen E ^a,c  

^a ANIMAL HEALTH TRUST   (United Kingdom)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; ASPARAGINE; CHEMOKINE RECEPTOR; CHEMOKINE RECEPTOR HOMOLOG M33 PROTEIN; MEMBRANE RECEPTOR; PHOSPHATIDYLINOSITOL; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; CYTOMEGALOVIRUS; GENE; GENE MUTATION; GENETIC CONSERVATION; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IN VIVO STUDY; M33 GENE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN MOTIF; RECEPTOR UPREGULATION; SALIVARY GLAND; SIGNAL TRANSDUCTION; UL33 GENE; VIRUS ATTENUATION; VIRUS GENE; VIRUS REPLICATION;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; ANIMALS; CELL MEMBRANE; CONSERVED SEQUENCE; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; MICE; MUROMEGALOVIRUS; NFATC TRANSCRIPTION FACTORS; PHOSPHATIDYLINOSITOLS; POINT MUTATION; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, CHEMOKINE; SALIVARY GLANDS; SIGNAL TRANSDUCTION; VIRAL PROTEINS; VIRUS REPLICATION;

MAIZE CHLOROTIC MOTTLE VIRUS; MURID HERPESVIRUS 1;

EID: 38949138811     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.02550-06     Document Type: Article

References (71)

1. Baldwin, J. M. 1993. The probable arrangement of the helices in G protein-coupled receptors. EMBO J. 12:1693-1703.
2. Ballesteros, J., S. Kitanovic, F. Guarnieri, P. Davies, B. J. Fromme, K. Konvicka, L. Chi, R. P. Millar, J. S. Davidson, H. Weinstein, and S. C. Sealfon. 1998. Functional microdomains in G protein-coupled receptors. The conserved arginine-cage motif in the gonadotropin-releasing hormone receptor. J. Biol. Chem. 273:10445-10453.
3. Ballesteros, J. A., A. D. Jensen, G. Liapakis, S. G. Rasmussen, L. Shi, U. Gether, and J. A. Javitch. 2001. Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J. Biol. Chem. 276:29171-29177.
4. Beisser, P. S., C. Vink, J. G. Van Dam, G. Grauls, S. J. Vanherle, and C. A. Bruggeman. 1998. The R33 G protein-coupled receptor gene of rat cytomegalovirus plays an essential role in the pathogenesis of viral infection. J. Virol. 72:2352-2363.
5. Bentz, G. L., M. Jarquin-Pardo, G. Chan, M. S. Smith, C. Sinzger, and A. D. Yurochko. 2006. Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive monocyte extravasation and transfer of productive virus to enhance hematogenous dissemination of HCMV. J. Virol. 80:11539-11555.
6. Blanpain, C., V. Wittamer, J. M. Vanderwinden, A. Boom, B. Renneboog, B. Lee, E. Le Poul, L. El Asmar, C. Govaerts, G. Vassart, R. W. Doms, and M. Parmentier. 2001. Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways. J. Biol. Chem. 276:23795-23804.
7. Bulenger, S., S. Marullo, and M. Bouvier. 2005. Emerging role of homo- and heterodimerization in G protein-coupled receptor biosynthesis and maturation. Trends Pharmacol. Sci. 26:131-137.
8. Burger, M., J. A. Burger, R. C. Hoch, Z. Oades, H. Takamori, and I. U. Schraufstatter. 1999. Point mutation causing constitutive signaling of CXCR2 leads to transforming activity similar to Kaposi's sarcoma herpesvirus-G protein-coupled receptor. J. Immunol. 163:2017-2022.
9. Capra, V., A. Veltri, C. Foglia, L. Crimaldi, A. Habib, M. Parenti, and G. E. Rovati. 2004. Mutational analysis of the highly conserved ERY motif of the thromboxane A2 receptor: alternative role in G protein-coupled receptor signaling. Mol. Pharmacol. 66:880-889.
10. Casarosa, P., Y. K. Gruijthuijsen, D. Michel, P. S. Beisser, J. Holl, C. P. Fitzsimons, D. Verzijl, C. A. Bruggeman, T. Mertens, R. Leurs, C. Vink, and M. J. Smit. 2003. Constitutive signaling of the human cytomegalovirus-encoded receptor UL33 differs from that of its rat cytomegalovirus homolog R33 by promiscuous activation of G proteins of the Gq, Gi, and Gs classes. J. Biol. Chem. 278:50010-50023.
11. Ceresa, B. P., and L. E. Limbird. 1994. Mutation of an aspartate residue highly conserved among G protein-coupled receptors results in nonreciprocal disruption of alpha 2-adrenergic receptor-G protein interactions. A negative charge at amino acid residue 79 forecasts alpha 2A-adrenergic receptor sensitivity to allosteric modulation by monovalent cations and fully effective receptor/G protein coupling. J. Biol. Chem. 269:29557-29564.
12. Chabre, M., and M. le Maire. 2005. Monomeric G protein-coupled receptor as a functional unit. Biochemistry 44:9395-9403.
13. Chee, M. S., S. C. Satchwell, E. Preddie, K. M. Weston, and B. G. Barrell. 1990. Human cytomegalovirus encodes three G protein-coupled receptor homologues. Nature 344:774-777.
14. Chen, A., Z. G. Gao, D. Barak, B. T. Liang, and K. A. Jacobson. 2001. Constitutive activation of A(3) adenosine receptors by site-directed mutagenesis. Biochem. Biophys. Res. Commun. 284:596-601.
15. Couty, J. P., and M. C. Gershengorn. 2005. G protein-coupled receptors encoded by human herpesviruses. Trends Pharmacol. Sci. 26:405-411.
16. Davis-Poynter, N. J., D. M. Lynch, H. Vally, G. R. Shellam, W. D. Rawlinson, B. G. Barrell, and H. E. Farrell. 1997. Identification and characterization of a G protein-coupled receptor homolog encoded by murine cytomegalovirus. J. Virol. 71:1521-1529.
17. Deayton, J. R. 2001. Changing trends in cytomegalovirus disease in HIV-infected patients. Herpes 8:37-40.
18. de Jong, M. D., G. J. Galasso, B. Gazzard, P. D. Griffiths, D. A. Jabs, E. R. Kern, and S. A. Spector. 1998. Summary of the II International Symposium on Cytomegalovirus. Antiviral Res. 39:141-162.
19. Dong, C., C. M. Filipeanu, M. T. Duvernay, and G. Wu. 2007. Regulation of G protein-coupled receptor export trafficking. Biochim. Biophys. Acta 1768: 853-870.
20. Donnelly, D., S. Maudsley, J. P. Gent, R. N. Moser, C. R. Hurrell, and J. B. Findlay. 1999. Conserved polar residues in the transmembrane domain of the human tachykinin NK2 receptor: functional roles and structural implications. Biochem. J. 339:55-61.
21. Favre, N., F. Fanelli, M. Missotten, A. Nichols, J. Wilson, M. di Tiani, C. Rommel, and A. Scheer. 2005. The DRY motif as a molecular switch of the human oxytocin receptor. Biochemistry 44:9990-10008.
22. Filizola, M., and H. Weinstein. 2005. The study of G protein coupled receptor oligomerization with computational modeling and bioinformatics. FEBS J. 272:2926-2938.
23. Fraile-Ramos, A., T. N. Kledal, A. Pelchen-Matthews, K. Bowers, T. W. Schwartz, and M. Marsh. 2001. The human cytomegalovirus US28 protein is located in endocytic vesicles and undergoes constitutive endocytosis and recycling. Mol. Biol. Cell 12:1737-1749.
24. Fraile-Ramos, A., T. A. Kohout, M. Waldhoer, and M. Marsh. 2003. Endocytosis of the viral chemokine receptor US28 does not require beta-arrestins but is dependent on the clathrin-mediated pathway. Traffic 4:243-253.
25. Fraile-Ramos, A., A. Pelchen-Matthews, T. N. Kledal, H. Browne, T. W. Schwartz, and M. Marsh. 2002. Localization of HCMV UL33 and US27 in endocytic compartments and viral membranes. Traffic 3:218-232.
26. Frascaroli, G., S. Varani, B. Moepps, C. Sinzger, M. P. Landini, and T. Mertens. 2006. Human cytomegalovirus subverts the functions of monocytes, impairing chemokine-mediated migration and leukocyte recruitment. J. Virol. 80:7578-7589.
27. Gether, U., F. Asmar, A. K. Meinild, and S. G. Rasmussen. 2002. Structural basis for activation of G protein-coupled receptors. Pharmacol. Toxicol. 91:304-312.
28. Gompels, U. A., J. Nicholas, G. Lawrence, M. Jones, B. J. Thomson, M. E. Martin, S. Efstathiou, M. Craxton, and H. A. Macaulay. 1995. The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology 209:29-51.
29. Govaerts, C., C. Blanpain, X. Deupi, S. Ballet, J. A. Ballesteros, S. J. Wodak, G. Vassart, L. Pardo, and M. Parmentier. 2001. The TXP motif in the second transmembrane helix of CCR5. A structural determinant of chemokine-induced activation. J. Biol. Chem. 276:13217-13225.
30. Griffiths, P. D. 2002. Tomorrow's challenges for herpesvirus management: potential applications of valacyclovir. J. Infect. Dis. 186(Suppl. 1):S131-S137.
31. Gruijthuijsen, Y. K., E. V. Beuken, M. J. Smit, R. Leurs, C. A. Bruggeman, and C. Vink. 2004. Mutational analysis of the R33-encoded G protein-coupled receptor of rat cytomegalovirus: identification of amino acid residues critical for cellular localization and ligand-independent signalling. J. Gen. Virol. 85:897-909.
32. Gruijthuijsen, Y. K., P. Casarosa, S. J. Kaptein, J. L. Broers, R. Leurs, C. A. Bruggeman, M. J. Smit, and C. Vink. 2002. The rat cytomegalovirus R33-encoded G protein-coupled receptor signals in a constitutive fashion. J. Virol. 76:1328-1338.
33. Holst, P. J., M. M. Rosenkilde, D. Manfra, S. C. Chen, M. T. Wiekowski, B. Holst, F. Cifire, M. Lipp, T. W. Schwartz, and S. A. Lira. 2001. Tumorigenesis induced by the HHV8-encoded chemokine receptor requires ligand modulation of high constitutive activity. J. Clin. Investig. 108:1789-1796.
34. Horton, R. M., H. D. Hunt, S. N. Ho, J. K. Pullen, and L. R. Pease. 1989. Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 77:61-68.
35. Isegawa, Y., Z. Ping, K. Nakano, N. Sugimoto, and K. Yamanishi. 1998. Human herpesvirus 6 open reading frame U12 encodes a functional beta-chemokine receptor. J. Virol. 72:6104-6112.
36. Lu, Z. L., C. A. Curtis, P. G. Jones, J. Pavia, and E. C. Hulme. 1997. The role of the aspartate-arginine-tyrosine triad in the m1 muscarinic receptor: mutations of aspartate 122 and tyrosine 124 decrease receptor expression but do not abolish signaling. Mol. Pharmacol. 51:234-241.
37. McLean, K. A., P. J. Holst, L. Martini, T. W. Schwartz, and M. M. Rosenkilde. 2004. Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74. Virology 325: 241-251.
38. Melnychuk, R. M., P. Smith, C. N. Kreklywich, F. Ruchti, J. Vomaske, L. Hall, L. Loh, J. A. Nelson, S. L. Orloff, and D. N. Streblow. 2005. Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration. J. Virol. 79:10788-10795.
39. Miller, W. E., D. A. Houtz, C. D. Nelson, P. E. Kolattukudy, and R. J. Lefkowitz. 2003. G protein-coupled receptor (GPCR) kinase phosphorylation and beta-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus US28 GPCR. J. Biol. Chem. 278:21663-21671.
40. Mocarski, E. S., Jr. 2002. Immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion. Trends Microbiol. 10:332-339.
41. Morello, J. P., and M. Bouvier. 1996. Palmitoylation: a post-translational modification mat regulates signalling from G protein coupled receptors. Biochem. Cell Biol. 74:449-457.
42. Morin, D., N. Cotte, M. N. Balestre, B. Mouillac, M. Manning, C. Breton, and C. Barberis. 1998. The D136A mutation of the V2 vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities. FEBS Lett. 441:470-475.
43. Nicholas, J. 1996. Determination and analysis of the complete nucleotide sequence of human herpesvirus 7. J. Virol. 70:5975-5989.
44. Oliveira, L., A. C. Paiva, C. Sander, and G. Vriend. 1994. A common step for signal transduction in G protein-coupled receptors. Trends Pharmacol. Sci. 15:170-172.
45. Perlman, J. H., A. O. Colson, W. Wang, K. Bence, R. Osman, and M. C. Gershengorn. 1997. Interactions between conserved residues in transmembrane helices 1, 2, and 7 of the thyrotropin-releasing hormone receptor. J. Biol. Chem. 272:11937-11942.
46. Qanbar, R., and M. Bouvier. 2003. Role of palmitoylation/ depalmitoylation reactions in G protein-coupled receptor function. Pharmacol. Ther. 97:1-33.
47. Rasmussen, S. G., A. D. Jensen, G. Liapakis, P. Ghanouni, J. A. Javitch, and U. Gether. 1999. Mutation of a highly conserved aspartic acid in the beta2 adrenergic receptor: constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6. Mol. Pharmacol. 56:175-184.
48. Rawlinson, W. D., H. E. Farrell, and B. G. Barrell. 1996. Analysis of the complete DNA sequence of murine cytomegalovirus. J. Virol. 70:8833-8849.
49. Razonable, R. R., and C. V. Paya. 2003. Herpesvirus infections in transplant recipients: current challenges in the clinical management of cytomegalovirus and Epstein-Barr virus infections. Herpes 10:60-65.
50. Rosenkilde, M. M., T. N. Kledal, P. J. Holst, and T. W. Schwartz. 2000. Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74. J. Biol. Chem. 275:26309-26315.
51. Rosenkilde, M. M., T. N. Kledal, and T. W. Schwartz. 2005. High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3. Mol. Pharmacol. 68:11-19.
52. Rosenkilde, M. M., K. A. McLean, P. J. Holst, and T. W. Schwartz. 2004. The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G12/13 proteins but constitutive signaling only through Gi and G12/13 proteins. J. Biol. Chem. 279: 32524-32533.
53. Rosenkilde, M. M., M. Waldhoer, H. R. Luttichau, and T. W. Schwartz. 2001. Virally encoded 7TM receptors. Oncogene 20:1582-1593.
54. Sarkar, G., and S. S. Sommer. 1990. The "megaprimer" method of site-directed mutagenesis. BioTechniques 8:404-407.
55. Scheer, A., T. Costa, F. Fanelli, P. G. De Benedetti, S. Mhaouty-Kodja, L. Abuin, M. Nenniger-Tosato, and S. Cotecchia. 2000. Mutational analysis of the highly conserved arginine within the Glu/Asp-Arg-Tyr motif of the alpha(1b)-adrenergic receptor: effects on receptor isomerization and activation. Mol. Pharmacol. 57:219-231.
56. Scheer, A., F. Fanelli, T. Costa, P. G. De Benedetti, and S. Cotecchia. 1997. The activation process of the alpha1B-adrenergic receptor: potential role of protonation and hydrophobicity of a highly conserved aspartate. Proc. Natl. Acad. Sci. USA 94:808-813.
57. Scheer, A., F. Fanelli, T. Costa, P. G. De Benedetti, and S. Cotecchia. 1996. Constitutively active mutants of the alpha 1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation. EMBO J. 15: 3566-3578.
58. Schwartz, T. W. 1994. Locating ligand-binding sites in 7TM receptors by protein engineering. Curr. Opin. Biotechnol. 5:434-444.
59. Seibold, A., M. Dagarag, and M. Birnbaumer. 1998. Mutations of the DRY motif that preserve beta 2-adrenoceptor coupling. Receptors Channels 5:375-385.
60. Sherrill, J. D., and W. E. Miller. 2006. G protein-coupled receptor (GPCR) kinase 2 regulates agonist-independent Gq/11 signaling from the mouse cytomegalovirus GPCR M33. J. Biol. Chem. 281:39796-39805.
61. Streblow, D. N., C. N. Kreklywich, P. Smith, J. L. Soule, C. Meyer, M. Yin, P. Beisser, C. Vink, J. A. Nelson, and S. L. Orloff. 2005. Rat cytomegalovirus-accelerated transplant vascular sclerosis is reduced with mutation of the chemokine-receptor R33. Am. J. Transplant. 5:436-442.
62. Streblow, D. N., C. Soderberg-Naucler, J. Vieira, P. Smith, E. Wakabayashi, F. Ruchti, K. Mattison, Y. Altschuler, and J. A. Nelson. 1999. The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell 99:511-520.
63. van Cleef, K. W., M. J. Smit, C. A. Bruggeman, and C. Vink. 2006. Cytomegalovirus-encoded homologs of G protein-coupled receptors and chemokines. J. Clin. Virol. 35:343-348.
64. Venkatesan, S., A. Petrovic, M. Locati, Y. O. Kim, D. Weissman, and P. M. Murphy. 2001. A membrane-proximal basic domain and cysteine cluster in the C-terminal tail of CCR5 constitute a bipartite motif critical for cell surface expression. J. Biol. Chem. 276:40133-40145.
65. Vink, C., E. Beuken, and C. A. Bruggeman. 2000. Complete DNA sequence of the rat cytomegalovirus genome. J. Virol. 74:7656-7665.
66. Vischer, H. F., R. Leurs, and M. J. Smit. 2006. HCMV-encoded G protein-coupled receptors as constitutively active modulators of cellular signaling networks. Trends Pharmacol. Sci. 27:56-63.
67. Waldhoer, M., P. Casarosa, M. M. Rosenkilde, M. J. Smit, R. Leurs, J. L. Whistler, and T. W. Schwartz. 2003. The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis. J. Biol. Chem. 278:19473-19482.
68. Waldhoer, M., T. N. Kledal, H. Farrell, and T. W. Schwartz. 2002. Murine cytomegalovirus (CMV) M33 and human CMV US28 receptors exhibit similar constitutive signaling activities. J. Virol. 76:8161-8168.
69. Wess, J. 1998. Molecular basis of receptor/G protein-coupling selectivity. Pharmacol. Ther. 80:231-264.
70. Wilson, M. H., H. A. Highfield, and L. E. Limbird. 2001. The role of a conserved inter-transmembrane domain interface in regulating alpha(2a)-adrenergic receptor conformational stability and cell-surface turnover. Mol. Pharmacol. 59:929-938.
71. Zhu, S. Z., S. Z. Wang, J. Hu, and E. E. el-Fakahany. 1994. An arginine residue conserved in most G protein-coupled receptors is essential for the function of the m1 muscarinic receptor. Mol. Pharmacol. 45:517-523.