1887

Abstract

The cytoplasmic domains of several herpesviral glycoproteins encompass potential intracellular sorting signals. To analyse the function of the cytoplasmic domains of different pseudorabies virus (PrV) glycoproteins, hybrid proteins were constructed consisting of the extracellular and transmembrane domains of envelope glycoprotein D (gD) fused to the cytoplasmic tails of gB, gE or gM (designated gDB, gDE and gDM), all of which contain putative endocytosis motifs. gD is a type I membrane protein required for binding to and entry into target cells. Localization of hybrid proteins compared to full-length gB, gE and gM as well as carboxy-terminally truncated variants of gD was studied by confocal laser scanning microscopy. The function of gD hybrids was assayed by -complementation of a gD-negative PrV mutant. The carboxy-terminal domains of gB and gM directed a predominantly intracellular localization of gDB and gDM, while full-length gD and a tail-less gD mutant (gDc) were preferentially expressed on the cell surface. In contrast gDE, and a gDB lacking the putative gB endocytosis signal (gDBΔ29), were predominantly located in the plasma membrane. Despite the different intracellular localization, all tested proteins were able to complement infectivity of a PrV gD mutant. Cells which stably express full-length gD and plasma-membrane-associated gD hybrids exhibit a significant resistance to PrV infection, while cells expressing predominantly intracellularly located forms do not. This suggests that the assumed sequestration of receptors by gD, which is supposed to be responsible for the interference phenomenon, occurs at the cell surface.

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2001-01-01
2019-09-18
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References

  1. Alconada, A., Bauer, U., Sodeik, B. & Hoflack, B. ( 1999; ). Intracellular traffic of herpes simplex virus glycoprotein gE: characterization of the sorting signals required for its trans-Golgi network localization. Journal of Virology 73, 377-387.
    [Google Scholar]
  2. Brack, A. R., Dijkstra, J. M., Granzow, H., Klupp, B. G. & Mettenleiter, T. C. ( 1999; ). Inhibition of virion maturation by simultaneous deletion of glycoproteins E, I, and M of pseudorabies virus. Journal of Virology 73, 5364-5372.
    [Google Scholar]
  3. Brack, A. R., Klupp, B. G., Granzow, H., Tirabassi, R., Enquist, L. W. & Mettenleiter, T. C. ( 2000; ). Role of the cytoplasmic tail of pseudorabies virus glycoprotein E in virion formation. Journal of Virology 74, 4004-4016.[CrossRef]
    [Google Scholar]
  4. Cocchi, F., Lopez, M., Menotti, L., Aoubala, M., Dubreuil, P. & Campadelli-Fiume, G. ( 1998; ). The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D. Proceedings of the National Academy of Sciences, USA 95, 15700-15705.[CrossRef]
    [Google Scholar]
  5. Dasika, G. K. & Letchworth, G. J. ( 2000; ). Homologous and heterologous interference requires bovine herpesvirus-1 glycoprotein D at the cell surface during virus entry. Journal of General Virology 81, 1041-1049.
    [Google Scholar]
  6. Dijkstra, J. M., Visser, N., Mettenleiter, T. C. & Klupp, B. G. ( 1996; ). Identification and characterization of pseudorabies virus glycoprotein gM as a nonessential virion component. Journal of Virology 70, 5684-5688.
    [Google Scholar]
  7. Dijkstra, J. M., Fuchs, W., Mettenleiter, T. C. & Klupp, B. G. ( 1997; ). Identification and transcriptional analysis of pseudorabies virus UL6 to UL12 genes. Archives of Virology 142, 17-35.[CrossRef]
    [Google Scholar]
  8. Geraghty, R. J., Krummenacher, C., Cohen, G. H., Eisenberg, R. J. & Spear, P. G. ( 1998; ). Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280, 1618-1620.[CrossRef]
    [Google Scholar]
  9. Gerdts, V., Jöns, A. & Mettenleiter, T. C. ( 1999; ). Potency of an experimental DNA vaccine against Aujeszky’s disease in pigs. Veterinary Microbiology 66, 1-13.[CrossRef]
    [Google Scholar]
  10. Gershon, A. A., Sherman, D. L., Zhu, Z., Gabel, C. A., Ambron, R. T. & Gershon, M. D. ( 1994; ). Intracellular transport of newly synthesized varicella-zoster virus: final envelopment in the trans-Golgi network. Journal of Virology 68, 6372-6390.
    [Google Scholar]
  11. Ghosh, K. & Ghosh, H. P. ( 1999; ). Role of the membrane anchoring and cytoplasmic domains in intracellular transport and localization of viral glycoproteins. Biochemical Cell Biology 77, 165-178.[CrossRef]
    [Google Scholar]
  12. Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K. & Pease, L. R. ( 1989; ). Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77, 51-59.[CrossRef]
    [Google Scholar]
  13. Johnson, D. C., Burke, R. L. & Gregory, T. ( 1990; ). Soluble forms of herpes simplex virus glycoprotein D bind to a limited number of cell surface receptors and inhibit virus entry into cells. Journal of Virology 64, 2569-2576.
    [Google Scholar]
  14. Kaplan, A. S. & Vatter, A. E. ( 1959; ). A comparison of herpes simplex and pseudorabies viruses. Virology 182, 732-741.
    [Google Scholar]
  15. Klupp, B. G., Fuchs, W., Weiland, E. & Mettenleiter, T. C. ( 1997; ). Pseudorabies virus glycoprotein L is necessary for virus infectivity but dispensable for virion localization of glycoprotein H. Journal of Virology 71, 7687-7695.
    [Google Scholar]
  16. Krummenacher, C., Nicola, A. V., Whitbeck, J. C., Lou, H., Hou, W., Lambris, J. D., Geraghty, R. J., Spear, P. G., Cohen, G. H. & Eisenberg, R. J. ( 1998; ). Herpes simplex virus glycoprotein D can bind to poliovirus receptor- related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. Journal of Virology 72, 7064-7074.
    [Google Scholar]
  17. Lopez, M., Cocchi, F., Menotti, L., Avitabile, E., Dubreuil, P. & Campadelli-Fiume, G. ( 2000; ). Nectin2α (PRR2α or HveB) and nectin2δ are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D. Journal of Virology 74, 1267-1274.[CrossRef]
    [Google Scholar]
  18. Lukàcs, N., Thiel, H. J., Mettenleiter, T. C. & Rziha, H. J. ( 1985; ). Demonstration of three major species of pseudorabies virus glycoproteins and identification of a disulfide-linked glycoprotein complex. Journal of Virology 53, 166-173.
    [Google Scholar]
  19. Marks, M. S., Woodruff, L., Ohno, H. & Bonifacino, J. S. ( 1996; ). Protein targeting by tyrosine- and di-leucine-based signals: evidence for distinct saturable components. Journal of Cell Biology 135, 341-354.[CrossRef]
    [Google Scholar]
  20. Marsh, M. & McMahon, H. T. ( 1999; ). The structural era of endocytosis. Science 285, 215-220.[CrossRef]
    [Google Scholar]
  21. Mettenleiter, T. C. ( 1989; ). Glycoprotein gIII deletion mutants of pseudorabies virus are impaired in virus entry. Virology 171, 623-625.[CrossRef]
    [Google Scholar]
  22. Mettenleiter, T. C. ( 2000; ). Aujeszky’s disease (pseudorabies) virus: the virus and molecular pathogenesis – state of the art, June 1999. Veterinary Research 31, 99-115.
    [Google Scholar]
  23. Mettenleiter, T. C. & Rauh, I. ( 1990; ). A glycoprotein gX–β-galactosidase fusion gene as insertional marker for rapid identification of pseudorabies virus mutants. Journal of Virological Methods 30, 55-65.[CrossRef]
    [Google Scholar]
  24. Meyer, G. A. & Radsak, K. D. ( 2000; ). Identification of a novel signal sequence that targets transmembrane proteins to the nuclear envelope inner membrane. Journal of Biological Chemistry 275, 3857-3866.[CrossRef]
    [Google Scholar]
  25. Nixdorf, R., Schmidt, J., Karger, A. & Mettenleiter, T. C. ( 1999; ). Infection of Chinese hamster ovary cells by pseudorabies virus. Journal of Virology 73, 8019-8026.
    [Google Scholar]
  26. Nixdorf, R., Klupp, B. G., Karger, A. & Mettenleiter, T. C. ( 2000; ). Effects of truncation of the carboxy terminus of pseudorabies virus glycoprotein B on infectivity. Journal of Virology 74, 7137-7145.[CrossRef]
    [Google Scholar]
  27. Olson, J. K. & Grose, C. ( 1997; ). Endocytosis and recycling of varicella-zoster virus Fc receptor glycoprotein gE: internalization mediated by a YXXL motif in the cytoplasmic tail. Journal of Virology 71, 4042-4054.
    [Google Scholar]
  28. Olson, J. K., Santos, R. A. & Grose, C. ( 1998; ). Varicella-zoster virus glycoprotein gE: endocytosis and trafficking of the Fc receptor. Journal of Infectious Diseases 178, 2-6.[CrossRef]
    [Google Scholar]
  29. Petrovskis, E. A., Timmins, J. G. & Post, L. E. ( 1986; ). Use of lambda gt11 to isolate genes for two pseudorabies virus glycoproteins with homology to herpes simplex virus and varicella-zoster virus glycoproteins. Journal of Virology 60, 185-193.
    [Google Scholar]
  30. Petrovskis, E. A., Meyer, A. L. & Post, L. E. ( 1988; ). Reduced yield of infectious pseudorabies virus and herpes simplex virus from cell lines producing viral glycoprotein gp50. Journal of Virology 62, 2196-2199.
    [Google Scholar]
  31. Radsak, K., Eickmann, M., Mockenhaupt, T., Bogner, E., Kern, H., Eis-Hubinger, A. & Reschke, M. ( 1996; ). Retrieval of human cytomegalovirus glycoprotein B from the infected cell surface for virus envelopment. Archives of Virology 141, 557-572.[CrossRef]
    [Google Scholar]
  32. Rauh, I. & Mettenleiter, T. C. ( 1991; ). Pseudorabies virus glycoproteins gII and gp50 are essential for virus penetration. Journal of Virology 65, 5348-5356.
    [Google Scholar]
  33. Rea, T. J., Timmins, J. G., Long, G. W. & Post, L. E. ( 1985; ). Mapping and sequence of the gene for the pseudorabies virus glycoprotein which accumulates in the medium of infected cells. Journal of Virology 54, 21-29.
    [Google Scholar]
  34. Reschke, M., Reis, B., Noding, K., Rohsiepe, D., Richter, A., Mockenhaupt, T., Garten, W. & Radsak, K. ( 1995; ). Constitutive expression of human cytomegalovirus glycoprotein B (gpUL55) with mutagenized carboxy-terminal hydrophobic domains. Journal of General Virology 76, 113-122.[CrossRef]
    [Google Scholar]
  35. Robbins, A. K., Dorney, D. J., Wathen, M. W., Whealy, M. E., Gold, C., Watson, R. J., Holland, L. E., Weed, S. D., Levine, M. & Glorioso, J. C. ( 1987; ). The pseudorabies virus gII gene is closely related to the gB glycoprotein gene of herpes simplex virus. Journal of Virology 61, 2691-2701.
    [Google Scholar]
  36. Schmidt, J., Klupp, B. G., Karger, A. & Mettenleiter, T. C. ( 1997; ). Adaptability in herpesviruses: glycoprotein D-independent infectivity of pseudorabies virus. Journal of Virology 71, 17-24.
    [Google Scholar]
  37. Schröder, C., Linde, G., Fehler, F. & Keil, G. M. ( 1997; ). From essential to beneficial: glycoprotein D loses importance for replication of bovine herpesvirus 1 in cell culture Journal of Virology 71, 25-33.
    [Google Scholar]
  38. Steven, A. C. & Spear, P. G. ( 1997; ). Herpesvirus capsid assembly and envelopment. In Structural Biology of Viruses , pp. 312-351. Edited by W. Chiu, R. M. Burnett& R. Garcea. New York:Oxford University Press.
  39. Tirabassi, R. S. & Enquist, L. W. ( 1998; ). Role of envelope protein gE endocytosis in the pseudorabies virus life-cycle. Journal of Virology 72, 4571-4579.
    [Google Scholar]
  40. Tirabassi, R. S. & Enquist, L. W. ( 1999; ). Mutation of the YXXL endocytosis motif in the cytoplasmic tail of pseudorabies virus gE. Journal of Virology 73, 2717-2728.
    [Google Scholar]
  41. Tirabassi, R. S. & Enquist, L. W. ( 2000; ). Role of the pseudorabies virus gI cytoplasmic domain in neuroinvasion, virulence, and posttranslational N-linked glycosylation. Journal of Virology 74, 3505-3516.[CrossRef]
    [Google Scholar]
  42. Tirabassi, R. S., Townley, R. A., Eldridge, M. G. & Enquist, L. W. ( 1997; ). Characterization of pseudorabies virus mutants expressing carboxy- terminal truncations of gE: evidence for envelope incorporation, virulence, and neurotropism domains. Journal of Virology 71, 6455-6464.
    [Google Scholar]
  43. Trowbridge, I. S. ( 1991; ). Endocytosis and signals for internalization. Current Opinion in Cell Biology 3, 634–641 [erratum 3, 1062].[CrossRef]
    [Google Scholar]
  44. Trowbridge, I. S., Collawn, J. F. & Hopkins, C. R. ( 1993; ). Signal-dependent membrane protein trafficking in the endocytic pathway. Annual Review of Cell Biology 9, 129-161.[CrossRef]
    [Google Scholar]
  45. Tugizov, S., Maidji, E., Xiao, J., Zheng, Z. & Pereira, L. ( 1998; ). Human cytomegalovirus glycoprotein B contains autonomous determinants for vectorial targeting to apical membranes of polarized epithelial cells. Journal of Virology 72, 7374-7386.
    [Google Scholar]
  46. Tugizov, S., Maidji, E., Xiao, J. & Pereira, L. ( 1999; ). An acidic cluster in the cytosolic domain of human cytomegalovirus glycoprotein B is a signal for endocytosis from the plasma membrane. Journal of Virology 73, 8677-8688.
    [Google Scholar]
  47. van Zijl, M., van der Gulden, H., de Wind, N., Gielkens, A. & Berns, A. ( 1990; ). Identification of two genes in the unique short region of pseudorabies virus; comparison with herpes simplex virus and varicella-zoster virus. Journal of General Virology 71, 1747-1755.[CrossRef]
    [Google Scholar]
  48. Whitbeck, J. C., Peng, C., Lou, H., Xu, R., Willis, S. H., Ponce, D. L., Peng, T., Nicola, A. V., Montgomery, R. I., Warner, M. S., Soulika, A. M., Spruce, L. A., Moore, W. T., Lambris, J. D., Spear, P. G., Cohen, G. H. & Eisenberg, R. J. ( 1997; ). Glycoprotein D of herpes simplex virus (HSV) binds directly to HVEM, a member of the tumor necrosis factor receptor superfamily and a mediator of HSV entry. Journal of Virology 71, 6083-6093.
    [Google Scholar]
  49. Whitbeck, J. C., Muggeridge, M. I., Rux, A. H., Hou, W., Krummenacher, C., Lou, H., van Geelen, A., Eisenberg, R. J. & Cohen, G. H. ( 1999; ). The major neutralizing antigenic site on herpes simplex virus glycoprotein D overlaps a receptor-binding domain. Journal of Virology 73, 9879-9890.
    [Google Scholar]
  50. Zhu, Z., Gershon, M. D., Hao, Y., Ambron, R. T., Gabel, C. A. & Gershon, A. A. ( 1995; ). Envelopment of varicella-zoster virus: targeting of viral glycoproteins to the trans-Golgi network. Journal of Virology 69, 7951-7959.
    [Google Scholar]
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