1887

Abstract

Glycoprotein H/glycoprotein L (gH/gL) complexes of herpesviruses are required for fusion of infecting virions with host cell membranes. In human cytomegalovirus (HCMV), neutralizing monoclonal antibodies (MAb) specific for gH inhibit the transfer of a fluorescent probe to the host cell from labelled virus particles. In similar fashion, in the present study, neutralizing gH-specific MAb inhibited HCMV- induced fusion-from-without in monolayers of both human embryonic fibroblasts and continuous astrocytoma cells (U373). No fusion was detected in cells co-infected with defective recombinant adenovirus vectors that elicited high-level expression of gH and gL, indicating that surface-expressed gH was not intrinsically fusogenic. However, when such cells were superinfected with HCMV that gave fusion- from-without, the resulting cell-to-cell fusion was considerably enhanced. Thus, under our experimental conditions, gH/gL on the cell surface functioned to increase membrane fusion once this was initiated by other components in the virus envelope.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-4-855
1998-04-01
2024-05-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/4/9568982.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-4-855&mimeType=html&fmt=ahah

References

  1. Babic N., Klupp B. G., Makoschey B., Karger A., Flamand A., Mettenleiter T. C. 1996; Glycoprotein gH of pseudorabies virus is essential for penetration and propagation in cell culture and in the nervous system of mice. Journal of General Virology 77:2277–2285
    [Google Scholar]
  2. Baboonian C., Blake K., Booth J. C., Wiblin C. N. 1989; Complement-independent neutralising monoclonal antibody with differential reactivity for strains of cytomegalovirus. Journal of Medical Virology 29:139–145
    [Google Scholar]
  3. Bold S., Ohlin M., Garten W., Radsak K. 1996; Structural domains involved in human cytomegalovirus glycoprotein B-mediated cell-cell fusion. Journal of General Virology 77:2297–2302
    [Google Scholar]
  4. Booth J. C., Beesley J. E., Stern H. 1978; Syncytium formation caused by human cytomegalovirus in human embryonic lung fibroblasts. Archives of Virology 57:143–152
    [Google Scholar]
  5. Britt W. J. 1996; Vaccines against human cytomegalovirus: time to test. Trends in Microbiology 4:34–38
    [Google Scholar]
  6. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchinson C. A., Kouzarides T., Martignetti J. A., Preddie E., Satchwell S. C., Tomlinson P., Weston K. M., Barrell B. G. 1990; Analysis of the protein coding content of the sequence of human cytomegalovirus strain AD169. Current Topics in Microbiology and Immunology 154:125–169
    [Google Scholar]
  7. Cranage M. P., Smith G. L., Bell S. E., Hart H., Brown C., Bankier A. T., Tomlinson P., Barrell B. G., Minson T. C. 1988; Identification and expression of a human cytomegalovirus glycoprotein with homology to the Epstein-Barr virus BXLF2 product, varicella-zoster virus gplll, and herpes simplex virus glycoprotein H. Journal of Virology 62:1416–1422
    [Google Scholar]
  8. Desai P. J., Schaffer P. A., Minson A. C. 1988; Excretion of noninfectious virus particles lacking glycoprotein H by a temperature-sensitive mutant of herpes simplex virus type 1 : evidence that gH is essential for virion infectivity. Journal of General Virology 69:1147–1156
    [Google Scholar]
  9. Duus K. M., Hatfield C., Grose C. 1995; Cell surface expression and fusion by the varicella-zoster virus gH: gL glycoprotein complex: analysis by laser scanning confocal microscopy. Virology 210:429–440
    [Google Scholar]
  10. Elek S. D., Stern H. 1974; Development of a vaccine against mental retardation caused by cytomegalovirus infection in utero . Lancet i:1–5
    [Google Scholar]
  11. Falconer M. M., Gilbert J. K., Roper A. M., Greenberg H. B., Gavora J. S. 1995; Rotavirus-induced fusion from without in tissue culture cells. Journal of Virology 69:5582–5591
    [Google Scholar]
  12. Falke D., Knoblich A., Müller S. 1985; Fusion from without induced by herpes simplex virus type 1. Intervirology 24:211–219
    [Google Scholar]
  13. Fernando S., Pearce M. J., Booth J. C. 1993; Lymphocyte responses and virus excretion as risk factors for intrauterine infection with human cytomegalovirus. Journal of Medical Virology 41:108–113
    [Google Scholar]
  14. Forrester A., Farrell H., Wilkinson G., Kaye J., Davis-Poynter N., Minson T. 1992; Construction and properties of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. Journal of Virology 66:341–348
    [Google Scholar]
  15. Garnett H. M. 1979; Fusion of cytomegalovirus infected fibroblasts to form multinucleated giant cells. Journal of Medical Virology 3:271–274
    [Google Scholar]
  16. Gompels U. A., Minson A. C. 1989; Antigenic properties and cellular localization of herpes simplex virus glycoprotein H synthesized in amammalian cell expression system. Journal of Virology 63:4744–4755
    [Google Scholar]
  17. Graham F. L., van der Eb A. J. 1974; A new technique for the assay of infectivity of adenovirus type 5 DNA. Virology 52:456–467
    [Google Scholar]
  18. Gretch D. R., Kari B., Rasmussen L., Gehrz R. C., Stinski M. F. 1988; Identification and characterization of three distinct families of glycoprotein complexes in the envelopes of human cytomegalovirus. Journal of Virology 62:875–881
    [Google Scholar]
  19. Huber M. T., Compton T. 1997; Characterisation of a novel third member of the human cytomegalovirus glycoprotein H-glycoprotein L complex. Journal of Virology 71:5391–5398
    [Google Scholar]
  20. Jacobs S. C., Stephenson J. R., Wilkinson G. W. G. 1992; High level expression of the tick-borne encephalitis virus NS1 protein by using an adenovirus-based vector: protection elicited in a murine model. Journal of Virology 66:2086–2095
    [Google Scholar]
  21. Kaye J. F., Gompels U. A., Minson A. C. 1992; Glycoprotein H of human cytomegalovirus (HCMV) forms a stable complex with the HCMV UL115 gene product. Journal of General Virology 73:2693–2698
    [Google Scholar]
  22. Keay S., Baldwin B. 1991; Anti-idiotype antibodies that mimic gp86 of human cytomegalovirus inhibit viral fusion but not attachment. Journal of Virology 65:5124–5128
    [Google Scholar]
  23. Keay S., Merigan T. C., Rasmussen L. 1989; Identification of cell surface receptors for the 86-kilodalton glycoprotein of human cyto-megalovirus. Proceedings of the National Academy of Sciences, USA 86:10100–10103
    [Google Scholar]
  24. Keay S., Baldwin B. R., Smith M. W., Wasserman S. S., Goldman W. F. 1991; Increases in [Ca2+]i mediated by the 92·5-kDa putative cell membrane receptor for HCMV gp86. American Journal of Physiology 269: Cell Physiology 38 C11–C21
    [Google Scholar]
  25. Li L., Nelson J., Britt W. J. 1997; Glycoprotein H-related complexes of human cytomegalovirus : identification of a third protein in the gCIII complex. Journal of Virology 71:3090–3097
    [Google Scholar]
  26. Liu D. X., Gompels U. A., Foa-Tomasi L., Campadelli-Fiume G. 1993; Human herpesvirus-6 glycoprotein H and L homologs are components of the gp100 complex and the gH external domain is the target for neutralizing monoclonal antibodies. Virology 197:12–22
    [Google Scholar]
  27. McGrory W. J., Bautista D. S., Graham F. L. 1988; A simple technique for the rescue of early region 1 mutations into infectious human adenovirus type 5. Virology 163:614–617
    [Google Scholar]
  28. Miller N. M., Hutt-Fletcher L. M. 1988; A monoclonal antibody to glycoprotein gp85 inhibits fusion but not attachment of Epstein-Barr virus. Journal of Virology 62:2366–2372
    [Google Scholar]
  29. Milne R. S. B. 1996 The glycoprotein H/L complex of human cytomegalovirus: its role in the spread of infection PhD thesis University of London, UK:
    [Google Scholar]
  30. Navarro D., Paz P., Tugizov S., Topp K., La Vail J., Pereira L. 1993; Glycoprotein B of human cytomegalovirus promotes virion penetration into cells, transmission of infection from cell-to-cell, and fusion of infected cells. Virology 197:143–158
    [Google Scholar]
  31. Nelson P. N., Rawal B. K., Boriskin Y. S., Mathers K., Powles R. L., Steel H. M., Tryhorn Y. S., Butcher P. D., Booth J. C. 1996; A polymerase chain reaction to detect a spliced late transcript of human cytomegalovirus in the blood of bone marrow transplant recipients. Journal of Virological Methods 56:139–148
    [Google Scholar]
  32. Pachl C., Probert W. S., Hermsen K. M., Masiarz F. R., Rasmussen L., Merigan T. C., Spaete R. R. 1989; The human cytomegalovirus strain Towne glycoprotein H gene encodes glycoprotein gp86. Virology 169:418–426
    [Google Scholar]
  33. Rasmussen L. E., Nelson R. M., Kelsall D. C., Merigan T. C. 1984; Murine monoclonal antibody to a single protein neutralises the infectivity of human cytomegalovirus. Proceedings of the National Academy of Sciences, USA 81:876–880
    [Google Scholar]
  34. Rasmussen L., Resta S., Merigan T. 1991; Human cytomegalovirus glycoprotein-receptor interactions. Transplantation Proceedings 23:60–63
    [Google Scholar]
  35. Riddell S. R., Rabin M., Geballe A. P., Britt W. J., Greenberg P. D. 1991; Class I MHC-restricted CTL recognition of cells infected with HCMV does not require endogenous viral gene expression. Journal of Immunology 146:2795–2804
    [Google Scholar]
  36. Roop C., Hutchinson L., Johnson D. C. 1993; A mutant herpes simplex virus type 1 unable to express glycoprotein L cannot enter cells, and its particles lack glycoprotein H. Journal of Virology 67:2285–2297
    [Google Scholar]
  37. Simpson J. A., Chow J. C., Baker J., Avdalovic N., Yuan S., Au D., Co M. S., Vasquez M., Britt W. J., Coelingh K. L. 1993; Neutralizing monoclonal antibodies that distinguish three antigenic sites on human cytomegalovirus glycoprotein H have conformationally distinct binding sites. Journal of Virology 67:489–496
    [Google Scholar]
  38. Spaete R. R., Perot K., Scott P. I., Nelson J. A., Stinski M. F., Pachl C. 1993; Coexpression of truncated cytomegalovirus gH with the UL115 gene product or the truncated human fibroblast growth factor receptor results in transport of gH to the cell surface. Virology 193:853–861
    [Google Scholar]
  39. Spear P. G. 1993; Membrane fusion induced by herpes simplex virus. In Viral Fusion Mechanisms pp. 201–232 Bentz J. Edited by Boca Raton: CRC Press;
    [Google Scholar]
  40. Steel H. M., Booth J. C., Tryhorn Y. S., Stern H. 1988; A simple immunoalkaline phosphatase method for the rapid diagnosis of cytomegalovirus (CMV) infection. Serodiagnosis and Immunotherapy in Infectious Disease 2:193–200
    [Google Scholar]
  41. Taylor-Wiedeman J., Sissons J. G. P., Borysiewicz L. K., Sinclair J. H. 1991; Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. Journal of General Virology 72:2059–2064
    [Google Scholar]
  42. Tevithia M. J., Spector D. J. 1984; Complementation of an adenovirus 5 immediate early mutant by cytomegalovirus. Virology 137:428–431
    [Google Scholar]
  43. Tevithia M. J., Spector D. J., Leisure K. M., Stinski M. F. 1987; Participation of two human cytomegalovirus immediate early gene regions in transcriptional activation of adenovirus promoters. Virology 161:276–285
    [Google Scholar]
  44. Tugizov S., Navarro D., Paz P., Wang Y., Qadri I., Pereira L. 1994; Function of human cytomegalovirus glycoprotein B: syncytium formation in cells constitutively expressing gB is blocked by virus neutralizing antibodies. Virology 201:263–276
    [Google Scholar]
  45. van Drunen Littel-van den Hurk S., Khattar S., Tikoo S. K., Babiuk L. A., Baranowski E., Plainchamp D., Thiry E. 1996; Glycoprotein H (gII/gp108) and glycoprotein L form a functional complex which plays a role in penetration, but not in attachment, of bovine herpesvirus 1. Journal of General Virology 77:1515–1520
    [Google Scholar]
  46. Vinogradskaya G. R., Goryshin I. Y., Berlin Y. A., Lanzov V. A. 1995; Optimization of PCR-based diagnostics for human cytomegalovirus. Journal of Virological Methods 53:103–112
    [Google Scholar]
  47. Walev I., Wollert K. C., Weisem K., Falke D. 1991; Characterisation of fusion from without induced by herpes simplex virus. Archives of Virology 117:29–44
    [Google Scholar]
  48. Wigler M., Silverstein S., Lee L. S., Pellicer A, Cheng Y.-C., Axel R. 1977; Transfer of purified herpesvirus thymidine kinase gene to cultured mouse cells. Cell 11:223–232
    [Google Scholar]
  49. Wilkinson G. W., Akrigg A. 1992; Constitutive and enhanced expression from the CMV major IE promoter in a defective adenovirus vector. Nucleic Acids Research 20:2233–2239
    [Google Scholar]
  50. Wilson D. W., Davis-Poynter N., Minson A. C. 1994; Mutations in the cytoplasmic tail of herpes simplex virus glycoprotein H suppress cell fusion by a syncytial strain. Journal of Virology 68:6985–6993
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-4-855
Loading
/content/journal/jgv/10.1099/0022-1317-79-4-855
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error