Abstract
A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion, cellular reprogramming, tissue targeting or for cell entry. Through their efficient evolutionary machinery and through in vivo selection performed directly on the human cellular and molecular targets, virus have been able to optimize the encoded receptors for distinct pharmacological profiles to help in various parts of the viral life cyclus. Most of the receptors encoded by human pathogenic virus are still orphan receptors, i.e. the endogenous ligand is unknown. In the few cases where it has been possible to characterize these receptors pharmacologically, they have been found to bind a broad spectrum of either CC chemokines, US28 from human cytomegalovirus, or CXC chemokines, ORF74 from human herpesvirus 8. Nevertheless, US28 has been specifically optimized for recognition of the membrane bound chemokine, fractalkine, conceivably involved in cell–cell transfer of virus; whereas ORF74 among the endogenous CXC chemokines has selected angiogenic chemokines as agonists and angiostatic/modulatory chemokines as inverse agonists. ORF74 possess substantial cell-transforming properties and signals with high constitutive activity through the phospholipase C and MAP kinase pathways. Interestingly, transgenic expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ahuja SK, Murphy PM . 1993 J. Biol. Chem. 268: 20691–20694
Ahuja SK, Murphy PM . 1999 Chemokines in Disease Herbert CA. (ed.) Humana Press Inc: Totowa, NJ pp. 235–251
Arvanitakis L, Geras-Raaka E, Varma A, Gershengorn MC, Cesarman E . 1997 Nature 385: 347–350
Bais C, Santomasso B, Coso O, Arvanitakis L, Raaka EG, Gutkind JS, Asch AS, Cesarman E, Gerhengorn MC, Mesri EA . 1998 Nature 391: 86–89
Beisser PS, Grauls G, Bruggeman CA, Vink C . 1999 J. Virol. 73: 7218–7230
Beisser PS, Vink C, Van Dam JG, Grauls G, Vanherle SJ, Bruggeman CA . 1998 J. Virol. 72: 2352–2363
Billstrom MA, Johnson GL, Avdi NJ, Scott Worthen G . 1998 J. Virol. 72: 5535–5544
Billstrom MA, Lehman LA, Scott Worthen G . 1999 Am. J. Respir. Cell. Mol. Biol. 21: 163–167
Birkenbach M, Josefsen K, Yalamanchili R, Lenoir G, Kieff E . 1993 J. Virol. 67: 2209–2220
Bodaghi B, Jones TR, Zipeto D, Vita C, Sun L, Laurent L, Arenzana-Seisdedos F, Virelizier JL, Michelson S . 1998 J. Exp. Med. 188: 855–866
Boshoff C . 1998 Nature 391: 24–25
Bräuner-Osborne H, Brann MR . 1996 Eur. J. Pharmacol. 295: 93–102
Campadelli-Fiume G, Mirandola P, Menotti L . 1999 Emerg. Infect. Dis. 5: 353–366
Carlquist JF, Edelman L, Bennion DW, Anderson JL . 1999 J. Infect. Dis. 179: 1094–1100
Casarosa P, Bakker RA, Verzijl D, Navis M, Timmerman H, Leurs R, Smit MJ . 2001 J. Biol. Chem. 276: 1133–1137
Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM . 1995 N. Engl. J. Med. 332: 1186–1191
Cesarman E, Nador RG, Bai F, Bohenzky RA, Russo JJ, Moore PS, Chang Y, Knowles DM . 1996 J. Virol. 70: 8218–8223
Challoner PB, Smith KT, Parker JD, MacLeod DL, Coulter SN, Rose TM, Schultz ER, Bennett L, Garber RL, Chang M, Schad PA, Stewart PM, Nowinski RC, Brown JP, Burmer GC . 1995 Proc. Natl. Acad. Sci. USA 92: 7440–7444
Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS . 1994 Science 266: 1865–1869
Chen S, Bacon KB, Li L, Garcia GE, Xia Y, Lo D, Thompson DA, Siani MA, Yamamoto T, Harrison JK, Feng L . 1998 J. Exp. Med. 188: 193–198
Clambey ET, Virgin HW, Speck SH . 2000 J. Virol. 74: 1973–1984
Daibata M, Taguchi T, Kamioka M, Kubonishi I, Taguchi H, Miyoshi I . 1998 Leukemia 12: 1002–1004
Daibata M, Taguchi T, Nemoto Y, Taguchi H, Miyoshi I . 1999 Blood 94: 1545–1549
Dairaghi DJ, Fan RA, McMaster BE, Hanley MR, Schall TJ . 1999 J. Biol. Chem. 274: 21569–21574
Dairaghi DJ, Greaves DR, Schall TJ . 1998 Sem. Virol. 8: 377–385
Damon I, Murphy PM, Moss B . 1998 Proc. Natl. Acad. Sci. USA 95: 6403–6407
Davis-Poynter NJ, Lynch DM, Vally H, Shellam GR, Rawlinson WD, Barrell BG, Farrell HE . 1997 J. Virol. 71: 1521–1529
Dupin N, Fisher C, Kellam P, Ariad S, Tulliez M, Franck N, van Marck E, Salmon D, Gorin I, Escande JP, Weiss RA, Alitalo K, Boshoff C . 1999 Proc. Natl. Acad. Sci. USA 96: 4546–4551
Enbom M, Wang FZ, Fredrikson S, Martin C, Dahl H, Linde A . 1999 Clin. Diagn. Lab. Immunol. 6: 545–549
Endres MJ, Garlisi CG, Xiao H, Shan L, Hedrick JA . 1999 J. Exp. Med. 189: 1993–1998
Flore O, Rafii S, Ely S, O'Leary JJ, Hyjek EM, Cesarman E . 1998 Nature 394: 588–592
Fong AM, Erickson HP, Zachariah JP, Poon S, Schamberg NJ, Imai T, Patel DD . 2000 J. Biol. Chem. 275: 3781–3786
Förster R, Schubel A, Breitfeld D, Kremmer E, Renner-Müller I, Wolf E, Lipp M . 1999 Cell 99: 23–33
Gao JL, Murphy PM . 1994 J. Biol. Chem. 269: 28539–28542
Gao S-J, Kingsley L, Li M, Zheng W, Parravicini C, Ziegler J, Newton R, Rinaldo CR, Saah A, Phair J, Detels R, Chang Y, Moore PS . 1996 Nature Med. 2: 925–928
Geras-Raaka E, Varma A, Clark-Lewis I, Gershengorn MC . 1998a Biochem. Biophys. Res. Comm. 253: 725–727
Geras-Raaka E, Varma A, Ho H, Clark-Lewis I, Gershengorn MC . 1998b J. Exp. Med. 188: 405–408
Gershengorn MC, Geras-Raaka E, Varma A, Clark-Lewis I . 1998 J. Clin. Invest. 102: 1469–1472
Gompels UA, Nicholas J, Lawrence G, Jones M, Thomson BJ, Martin MED, Efstathiou S, Craxton M, Macaulay HA . 1995 Virology 209: 29–51
Guo H-G, Browning P, Nicholas J, Hayward GS, Tschachler E, Jiang YW, Sadowska M, Raffeld M, Colombini S, Gallo RC, Reitz Jr MS . 1997 Virology 228: 371–378
Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, Knott A, Dewhurst S, Insel RA, Epstein LG . 1994 N. Engl. J. Med. 331: 432–438
Hasegawa H, Utsunomiya Y, Yasukawa M, Yanagisawa K, Fujita S . 1994 J. Virol. 68: 5326–5329
Haskell CA, Cleary MD, Charo IF . 2000 J. Biol. Chem. 275: 34183–34189
Ho HH, Du D, Gershengorn MC . 1999 J. Biol. Chem. 274: 31327–31332
Horuk R . 1994 TiPS 15: 159–165
Isegawa Y, Ping Z, Nakano K, Sugimoto N, Yamanishi K . 1998 J. Virol. 72: 6104–6112
Julius D, Livelli TJ, Jessell TM, Axel R . 1989 Science 244: 1057–1062
Jung JU, Joong-Kook C, Ensser A, Biesinger B . 1999 Sem. Cancer Biol. 9: 231–239
Kirshner JR, Staskus K, Haase A, Lagunoff M, Ganem D . 1999 J. Virol. 73: 6006–6014
Kledal TN, Rosenkilde MM, Coulin F, Simmons G, Johnsen AH, Alouani S, Power CA, Lüttichau HR, Gerstoft J, Clapham PR, Clark LI, Wells TC, Schwartz TW . 1997 Science 277: 1656–1659
Kledal TN, Rosenkilde MM, Schwartz TW . 1998 FEBS Lett. 441: 209–214
Kuhn DE, Beall CJ, Kolattukudy PE . 1995 Biochem. Biophys. Res. Comm. 211: 325–330
Lalani AS, McFadden G . 1999 Cytokine Growth Factor Rev. 10: 219–233
Lee LF, Wu P, Sui D, Ren D, Kamil J, Kung HJ, Witter RL . 2000 Proc. Natl. Acad. Sci. USA 97: 6091–6096
Luppi M, Marasca R, Barozzi P, Ferrari S, Ceccherini-Nelli L, Batoni G, Merelli E, Torelli G . 1993 J. Med. Vir. 40: 44–52
Luppi M, Torelli G . 1996 Haematologica 81: 265–281
Lüttichau HR, Schwartz TW . 2000 Curr. Opin. Drug Discov. Dev. 3: 610–613
Lüttichau HR, Stine J, Boesen TP, Johnsen AH, Chantry D, Gerstoft J, Schwartz TW . 2000 J. Exp. Med. 191: 171–180
Margulies BJ, Browne H, Gibson W . 1996 Virology 225: 111–125
Matloubian M, David A, Engel S, Ryan JE, Cyster JG . 2000 Nat. Immunol. 1: 298–304
Melnick JL, Petrie BL, Dreesman GR, Burek J, McCollum CH, DeBakey ME . 1983 Lancet 2: 644–647
Menotti L, Mirandola P, Locati M, Campadelli-Fiume G . 1999 J. Virology 73: 325–333
Milne RS, Mattick C, Nicholson L, Devaraj P, Alcami A, Gompels UA . 2000 J. Immunol. 164: 2396–2404
Mirandola P, Stefan A, Brambilla E, Campadelli-Fiume G, Grimaldi LM . 1999 Neurology 53: 1367–1368
Moore BB, Arenberg DA, Strieter RM . 1998 Trends Cardiovasc. Sci. 8: 51–58
Munshi N, Ganju RK, Avraham S, Mesri EA, Groopman JE . 1999 J. Biol. Chem. 274: 31863–31867
Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, Power CA . 2000 Pharmacol. Rev. 52: 145–176
Neipel F, Albrecht J-C, Fleckenstein B . 1997 J. Virol. 71: 4187–4192
Nicholas J . 1996 J. Virol. 70: 5975–5989
Nieto FJ . 1999 Am Heart J. 138: S453–S460
Orenstein JM, Alkan S, Blauvelt A, Jeang KT, Weinstein MD, Ganem D, Herndier B . 1997 AIDS 11: F35–F45
Parravicini C, Chandran B, Corbellino M, Berti E, Paulli M, Moore PS, Chang Y . 2000 Am. J. Pathol. 156: 743–749
Parry CM, Simas JP, Smith VP, Stewart CA, Minson AC, Efstathiou S, Alcami A . 2000 J. Exp. Med. 191: 573–578
Penfold MET, Dairaghi DJ, Duke GM, Saederup N, Mocarski ES, Kemble GW, Schall TJ . 1999 Proc. Natl. Acad. Sci. USA 96: 9839–9844
Pleskoff O, Treboute C, Brelot A, Heveker N, Seman M, Alizon M . 1997 Science 276: 1874–1878
Pleskoff O, Tréboute C, Alizon M . 1998 J. Virol. 72: 6389–6397
Rollins BJ . 1998 Blood 90: 909–928
Rosenkilde MM, Kledal TN, Bräuner-Osborne H, Schwartz TW . 1999 J. Biol. Chem. 274: 956–961
Rosenkilde MM, Kledal TN, Holst PJ, Schwartz TW . 2000 J. Biol. Chem. 275: 26309–26915
Rosenkilde MM, Schwartz TW . 2000 Mol. Pharmacol. 57: 602–609
Russo JJ, Bohenzky RA, Chien M-C, Chen J, Yan M, Maddalena D, Parry JP, Peruzzi D, Edelman IS, Chang Y, Moore PS . 1996 Proc. Natl. Acad. Sci. USA 93: 14862–14867
Salahuddin SZ, Ablashi DV, Markham PD, Josephs SF, Sturzenegger S, Kaplan M, Halligan G, Biberfeld P, Wong-Staal F, Kramarsky B, Gallo RC . 1986 Science 234: 596–601
Schwartz TW . 1994 Curr. Opin. Biotech. 5: 434–444
Shibutani T, Johnson TM, Yu Z-X, Ferrans VJ, Moss J, Epstein SE . 1997 J. Clin. Invest. 100: 2054–2061
Simas JP, Efstathiou S . 1998 Trends Microbiol. 6: 276–282
Sodhi A, Montaner S, Patel V, Zohar M, Bais C, Mesri EA, Gutkind JS . 2000 Cancer Res. 60: 4873–4880
Soldan SS, Berti R, Salem N, Secchiero P, Flamand L, Calabresi PA, Brennan MB, Maloni HW, McFarland HF, Lin H-C, Patnaik M, Jacobson S . 1997 Nature Med. 3: 1394–1397
Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, d'Agay MF, Clauvel JP, Raphael M, Degos L . 1995 Blood 86: 1276–1280
Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, Renne R, Beneke J, Pudney J, Anderson DJ, Ganem D, Haase AT . 1997 J. Virol. 71: 715–719
Stine JT, Wood C, Hill M, Epp A, Raport CJ, Schweickart VL, Endo Y, Sasaki T, Simmons G, Boshoff C, Clapham P, Chang Y, Moore P, Gray PW, Chantry D . 2000 Blood 95: 1151–1157
Streblow DN, Soderberg-Naucler C, Vieira J, Smith P, Wakabayashi E, Ruchti F, Mattison K, Altschuler Y, Nelson JA . 1999 Cell 99: 511–520
Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, Dzuiba J, Van DJ, Walz A, Marriott D . 1995 J. Biol. Chem. 270: 27348–27357
Sun R, Lin S-F, Staskus K, Gradoville L, Grogan E, Hase E, Miller G . 1999 J. Virol. 73: 2232–2242
Van Berkel V, Barrett J, Tiffany HL, Fremont DH, Murphy PM, McFadden G, Speck SH, Virgin HW . 2000 J. Virol. 74: 6741–6747
Vieira J, Schall TJ, Corey L, Geballe AP . 1998 J. Virol. 72: 8158–8165
Wang JM, Shen W, Chertov O, Van Damme J, Oppenheim JJ . 1999 Chemokines and Cancer. Rollins BJ (ed.) Humana Press Inc pp. 129–141
Wells TNC, Schwartz TW . 1997 Curr. Opin. Biotech. 8: 741–748
Yang YT, Chen SC, Leach MW, Manfra D, Homey B, Wiekowski M, Sullivan L, Jenh CH, Narula SK, Chensue SW, Lira SA . 2000 J. Exp. Med. 191: 445–454
Yoshida R, Imai T, Hieshima K, Kusuda J, Baba M, Kitaura M, Nishimura M, Kakizaki M, Nomiyama H, Yoshie O . 1997 J. Biol. Chem. 272: 13803–13809
Zhou YF, Leon ML, Waclawiw MA, Popma JJ, Yu ZX, Finkel T, Epstein SE . 1996 N. Engl. J. Med. 335: 624–630
Zhu H, Cong JP, Mamtora G, Gingeras T, Shenk T . 1998 Proc. Natl. Acad. Sci. USA 95: 14470–14475
Zou P, Isegawa Y, Nakano K, Haque M, Horiguchi Y, Yamanishi K . 1999 J. Virol. 73: 5926–5933
Acknowledgements
Special thanks to François Talabot and Timothy Wells, Serono Research Group, Geneva, Switzerland for generation of basic information of the dendrograms presented in Figure 1. This study was supported by grants from the Danish Medical Research Council, the Danish Cancer Association, the Lundbeck Foundation (MM Rosenkilde, HR Lüttichau and TW Schwartz) and by an EMBO Fellowship (M Waldhoer).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rosenkilde, M., Waldhoer, M., Lüttichau, H. et al. Virally encoded 7TM receptors. Oncogene 20, 1582–1593 (2001). https://doi.org/10.1038/sj.onc.1204191
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204191
Keywords
This article is cited by
-
Emerging roles of cytomegalovirus-encoded G protein-coupled receptors during lytic and latent infection
Medical Microbiology and Immunology (2019)
-
Herpesvirus-encoded GPCRs: neglected players in inflammatory and proliferative diseases?
Nature Reviews Drug Discovery (2014)
-
Identification of G protein-coupled receptor signaling pathway proteins in marine diatoms using comparative genomics
BMC Genomics (2013)
-
Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors
British Journal of Pharmacology (2008)
-
Viral hijacking of G-protein-coupled-receptor signalling networks
Nature Reviews Molecular Cell Biology (2004)