1887

Abstract

Murine cytomegalovirus (MCMV) M78 is a member of the betaherpesvirus ‘UL78 family’ of seven transmembrane receptor (7TMR) genes. Previous studies of M78 and its counterpart in rat cytomegalovirus (RCMV) have suggested that these genes are required for efficient cell–cell spread of their respective viruses in tissue culture and demonstrated that gene knockout viruses are significantly attenuated for replication . However, in comparison with other CMV 7TMRs, relatively little is known about the basic biochemical properties and subcellular trafficking of the UL78 family members. We have characterized MCMV M78 in both transiently transfected and MCMV-infected cells to determine whether M78 exhibits features in common with cellular 7TMR. We obtained preliminary evidence that M78 formed dimers, a property that has been reported for several cellular 7TMR. M78 traffics to the cell surface, but was rapidly and constitutively endocytosed. Antibody feeding experiments demonstrated co-localization of M78 with markers for both the clathrin-dependent and lipid raft/caveolae-mediated internalization pathways. In MCMV-infected cells, the subcellular localization of M78 was modified during the course of infection, which may be related to the incorporation of M78 into the virion envelope during the course of virion maturation.

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2009-01-01
2019-11-13
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References

  1. Allan, J. E. & Shellam, G. R. ( 1984; ). Genetic control of murine cytomegalovirus infection: virus titres in resistant and susceptible strains of mice. Arch Virol 81, 139–150.[CrossRef]
    [Google Scholar]
  2. Beisser, P. S., Grauls, G., Bruggeman, C. A. & Vink, C. ( 1999; ). Deletion of the R78 G protein-coupled receptor gene from rat cytomegalovirus results in an attenuated, syncytium-inducing mutant strain. J Virol 73, 7218–7230.
    [Google Scholar]
  3. Bodaghi, B., Jones, T. R., Zipeto, D., Vita, C., Sun, L., Laurent, L., Arenzana-Seisdedos, F., Virelizier, J. L. & Michelson, S. ( 1998; ). Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells. J Exp Med 188, 855–866.[CrossRef]
    [Google Scholar]
  4. Bulenger, S., Marullo, S. & Bouvier, M. ( 2005; ). Emerging role of homo- and heterodimerization in G-protein-coupled receptor biosynthesis and maturation. Trends Pharmacol Sci 26, 131–137.[CrossRef]
    [Google Scholar]
  5. Casarosa, P., Bakker, R. A., Verzijl, D., Navis, M., Timmerman, H., Leurs, R. & Smit, M. J. ( 2001; ). Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J Biol Chem 276, 1133–1137.[CrossRef]
    [Google Scholar]
  6. Droese, J., Mokros, T., Hermosilla, R., Schulein, R., Lipp, M., Hopken, U. E. & Rehm, A. ( 2004; ). HCMV-encoded chemokine receptor US28 employs multiple routes for internalization. Biochem Biophys Res Commun 322, 42–49.[CrossRef]
    [Google Scholar]
  7. Fitzsimons, C. P., Gompels, U. A., Verzijl, D., Vischer, H. F., Mattick, C., Leurs, R. & Smit, M. J. ( 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, 888–898.
    [Google Scholar]
  8. Fraile-Ramos, A., Kledal, T. N., Pelchen-Matthews, A., Bowers, K., Schwartz, T. W. & Marsh, M. ( 2001; ). The human cytomegalovirus US28 protein is located in endocytic vesicles and undergoes constitutive endocytosis and recycling. Mol Biol Cell 12, 1737–1749.[CrossRef]
    [Google Scholar]
  9. Fraile-Ramos, A., Pelchen-Matthews, A., Kledal, T. N., Browne, H., Schwartz, T. W. & Marsh, M. ( 2002; ). Localization of HCMV UL33 and US27 in endocytic compartments and viral membranes. Traffic 3, 218–232.[CrossRef]
    [Google Scholar]
  10. Fraile-Ramos, A., Kohout, T. A., Waldhoer, M. & Marsh, M. ( 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.[CrossRef]
    [Google Scholar]
  11. Hanyaloglu, A. C. & von Zastrow, M. ( 2008; ). Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Annu Rev Pharmacol Toxicol 48, 537–568.[CrossRef]
    [Google Scholar]
  12. Kuhn, D. E., Beall, C. J. & Kolattukudy, P. E. ( 1995; ). The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity. Biochem Biophys Res Commun 211, 325–330.[CrossRef]
    [Google Scholar]
  13. Le, Y., Zhou, Y., Iribarren, P. & Wang, J. ( 2004; ). Chemokines and chemokine receptors: their manifold roles in homeostasis and disease. Cell Mol Immunol 1, 95–104.
    [Google Scholar]
  14. Mack, M., Luckow, B., Nelson, P. J., Cihak, J., Simmons, G., Clapham, P. R., Signoret, N., Marsh, M., Stangassinger, M. & other authors ( 1998; ). Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity. J Exp Med 187, 1215–1224.[CrossRef]
    [Google Scholar]
  15. Margulies, B. J. & 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.[CrossRef]
    [Google Scholar]
  16. Metzelaar, M. J., Wijngaard, P. L. J., Peters, P. J., Sixma, J. J., Nieuwenhuis, H. K. & Clevers, H. C. ( 1991; ). CD63 antigen: a novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells. J Biol Chem 266, 3239–3245.
    [Google Scholar]
  17. Milne, R. S., Mattick, C., Nicholson, L., Devaraj, P., Alcami, A. & Gompels, U. A. ( 2000; ). RANTES binding and down-regulation by a novel human herpesvirus-6 β chemokine receptor. J Immunol 164, 2396–2404.[CrossRef]
    [Google Scholar]
  18. Mocarski, E. S., Jr ( 2002; ). Immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion. Trends Microbiol 10, 332–339.[CrossRef]
    [Google Scholar]
  19. Nakamura, N., Rabouille, C., Watson, R., Nilsson, T., Hui, N., Slusarewicz, P., Kreis, T. E. & Warren, G. ( 1995; ). Characterization of a cis-Golgi matrix protein, GM130. J Cell Biol 131, 1715–1726.[CrossRef]
    [Google Scholar]
  20. Oliveira, S. A. & Shenk, T. E. ( 2001; ). Murine cytomegalovirus M78 protein, a G protein-coupled receptor homologue, is a constituent of the virion and facilitates accumulation of immediate-early viral mRNA. Proc Natl Acad Sci U S A 98, 3237–3242.[CrossRef]
    [Google Scholar]
  21. Pang, H., Le, P. U. & Nabi, I. R. ( 2004; ). Ganglioside GM1 levels are a determinant of the extent of caveolae/raft-dependent endocytosis of cholera toxin to the Golgi apparatus. J Cell Sci 117, 1421–1430.[CrossRef]
    [Google Scholar]
  22. Patki, V., Virbasius, J., Lane, W. S., Toh, B. H., Shpetner, H. S. & Corvera, S. ( 1997; ). Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A 94, 7326–7330.[CrossRef]
    [Google Scholar]
  23. Pelkmans, L. & Helenius, A. ( 2002; ). Endocytosis via caveolae. Traffic 3, 311–320.[CrossRef]
    [Google Scholar]
  24. Signoret, N., Pelchen-Matthews, A., Mack, M., Proudfoot, A. E. & Marsh, M. ( 2000; ). Endocytosis and recycling of the HIV coreceptor CCR5. J Cell Biol 151, 1281–1294.[CrossRef]
    [Google Scholar]
  25. Sinclair, J. & Sissons, P. ( 2006; ). Latency and reactivation of human cytomegalovirus. J Gen Virol 87, 1763–1779.[CrossRef]
    [Google Scholar]
  26. Tadagaki, K., Nakano, K. & Yamanishi, K. ( 2005; ). Human herpesvirus 7 open reading frames U12 and U51 encode functional β-chemokine receptors. J Virol 79, 7068–7076.[CrossRef]
    [Google Scholar]
  27. Vischer, H. F., Vink, C. & Smit, M. J. ( 2006; ). A viral conspiracy: hijacking the chemokine system through virally encoded pirated chemokine receptors. Curr Top Microbiol Immunol 303, 121–154.
    [Google Scholar]
  28. Yamashiro, D. J., Tycko, B., Fluss, S. R. & Maxfield, F. R. ( 1984; ). Segregation of transferrin to a mildly acidic (pH 6.5) para-Golgi compartment in the recycling pathway. Cell 37, 789–800.[CrossRef]
    [Google Scholar]
  29. Zhen, Z., Bradel-Tretheway, B., Sumagin, S., Bidlack, J. M. & 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, 11914–11924.[CrossRef]
    [Google Scholar]
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