1887

Abstract

The mechanisms by which herpes simplex viruses (HSV) mediate fusion between their envelope and the plasma membrane during entry into cells, and between the plasma membranes of adjacent infected and uninfected cells to form multinucleated giant cells, are poorly understood. Four viral glycoproteins (gB, gD, gH and gL) are required for virus–cell fusion, whereas these plus several others are required for cell–cell fusion (syncytium formation). A better understanding would be aided by the availability of a model system, whereby fusion could be induced with a minimal set of proteins, in the absence of infection. A suitable system has now been developed for HSV-2, using transfected COS7, 293 or HEp-2 cells. Insofar as the minimal set of HSV-2 proteins required to cause cell–cell fusion in this system is gB, gD, gH and gL, it would appear to resemble virus–cell fusion rather than syncytium formation. However, the ability of a mutation in gB to enhance the fusion of both transfected cells and infected cells, while having no effect on virus–cell fusion, points to the opposite conclusion. The differential effects of a panel of anti-HSV antibodies, and of the fusion-inhibitor cyclosporin A, confirm that the fusion of transfected cells shares some properties with virus–cell fusion and others with syncytium formation. It may therefore prove useful for determining how these processes differ, and for testing the hypothesis that some viral proteins prevent membrane fusion until the appropriate point in the virus life-cycle, with other proteins then overcoming this block.

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2000-08-01
2019-10-21
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References

  1. Andersson, S., Davis, D. N., Dahlback, H., Jornvall, H. & Russell, D. W. ( 1989; ). Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. Journal of Biological Chemistry 264, 8222-8229.
    [Google Scholar]
  2. Bentz, J. (1993). Viral Fusion Mechanisms. Boca Raton, FL: CRC Press.
  3. Blank, H., Burgoon, C. F., Baldridge, G. D., McCarthy, P. L. & Urbach, F. ( 1951; ). Cytologic smears in diagnosis of herpes simplex, herpes zoster, and varicella. Journal of the American Medical Association 146, 1410-1412.[CrossRef]
    [Google Scholar]
  4. Butcher, M., Raviprakash, K. & Ghosh, H. P. ( 1990; ). Acid pH-induced fusion of cells by herpes simplex virus glycoproteins gB and gD. Journal of Biological Chemistry 265, 5862-5868.
    [Google Scholar]
  5. Cai, W., Gu, B. & Person, S. ( 1988; ). Role of glycoprotein B of herpes simplex virus type 1 in viral entry and cell fusion. Journal of Virology 62, 2596-2604.
    [Google Scholar]
  6. Campadelli-Fiume, G., Avitabile, E., Fini, S., Stirpe, D., Arsenakis, M. & Roizman, B. ( 1988; ). Herpes simplex virus glycoprotein D is sufficient to induce spontaneous pH-independent fusion in a cell line that constitutively expresses the glycoprotein. Virology 166, 598-602.[CrossRef]
    [Google Scholar]
  7. Cocchi, F., Menotti, L., Mirandola, P., Lopez, M. & Campadelli-Fiume, G. ( 1998; ). The ectodomain of a novel member of the immunoglobulin superfamily related to the poliovirus receptor has the attributes of a bona fide receptor for herpes simplex virus types 1 and 2 in human cells. Journal of Virology 72, 9992-10002.
    [Google Scholar]
  8. Cohen, G. H., Isola, V. J., Kuhns, J., Berman, P. W. & Eisenberg, R. J. ( 1986; ). Localization of discontinuous epitopes of herpes simplex virus glycoprotein D: use of a nondenaturing (‘native’ gel) system of polyacrylamide gel electrophoresis coupled with Western blotting. Journal of Virology 60, 157-166.
    [Google Scholar]
  9. Davis-Poynter, N., Bell, S., Minson, T. & Browne, H. ( 1994; ). Analysis of the contributions of herpes simplex virus type 1 membrane proteins to the induction of cell-cell fusion. Journal of Virology 68, 7586-7590.
    [Google Scholar]
  10. Doane, F., Rhodes, A. J. & Ormsby, H. L. ( 1955; ). Tissue culture techniques in the study of herpetic infections of the eye. American Journal of Ophthalmology 40, 189-193.[CrossRef]
    [Google Scholar]
  11. Eisenberg, R. J., Long, D., Ponce de Leon, M., Matthews, J. T., Spear, P. G., Gibson, M. G., Lasky, L. A., Berman, P., Golub, E. & Cohen, G. H. ( 1985; ). Localization of epitopes of herpes simplex virus type 1 glycoprotein D. Journal of Virology 53, 634-644.
    [Google Scholar]
  12. Forrester, A., Farrell, H., Wilkinson, G., Kaye, J., Davis-Poynter, N. & Minson, T. ( 1992; ). Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. Journal of Virology 66, 341-348.
    [Google Scholar]
  13. Friedman, H. M., Cohen, G. H., Eisenberg, R. J., Seidel, C. A. & Cines, D. B. ( 1984; ). Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells. Nature 309, 633-635.[CrossRef]
    [Google Scholar]
  14. Fuller, A. O. & Spear, P. G. ( 1987; ). Anti-glycoprotein D antibodies that permit adsorption but block infection by herpes simplex virus 1 prevent virion-cell fusion at the cell surface. Proceedings of the National Academy of Sciences, USA 84, 5454-5458.[CrossRef]
    [Google Scholar]
  15. 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]
  16. Haanes, E. J., Nelson, C. M., Soule, C. L. & Goodman, J. L. ( 1994; ). The UL45 gene product is required for herpes simplex virus type 1 glycoprotein B-induced fusion. Journal of Virology 68, 5825-5834.
    [Google Scholar]
  17. Highlander, S. L., Sutherland, S. L., Gage, P. J., Johnson, D. C., Levine, M. & Glorioso, J. C. ( 1987; ). Neutralizing monoclonal antibodies specific for herpes simplex virus glycoprotein D inhibit virus penetration. Journal of Virology 61, 3356-3364.
    [Google Scholar]
  18. Huang, A. & Wagner, R. ( 1964; ). Penetration of herpes simplex virus into human epidermoid cells. Proceedings of the Society for Experimental Biology and Medicine 116, 863-869.[CrossRef]
    [Google Scholar]
  19. Hutchinson, L., Browne, H., Wargent, V., Davis-Poynter, N., Primorac, S., Goldsmith, K., Minson, A. C. & Johnson, D. C. ( 1992; ). A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH. Journal of Virology 66, 2240-2250.
    [Google Scholar]
  20. 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]
  21. 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]
  22. Ligas, M. W. & Johnson, D. C. ( 1988; ). A herpes simplex virus mutant in which glycoprotein D sequences are replaced by β-galactosidase sequences binds to but is unable to penetrate into cells. Journal of Virology 62, 1486-1494.
    [Google Scholar]
  23. McKenzie, R. C., Epand, R. M. & Johnson, D. C. ( 1987; ). Cyclosporine A inhibits herpes simplex virus-induced cell fusion but not virus penetration into cells. Virology 159, 1-9.[CrossRef]
    [Google Scholar]
  24. Marlin, S. D., Highlander, S. L., Holland, T. C., Levine, M. & Glorioso, J. C. ( 1986; ). Antigenic variation (mar mutations) in herpes simplex virus glycoprotein B can induce temperature-dependent alterations in gB processing & virus production. Journal of Virology 59, 142-153.
    [Google Scholar]
  25. Minson, A. C., Hodgman, T. C., Digard, P., Hancock, D. C., Bell, S. E. & Buckmaster, E. A. ( 1986; ). An analysis of the biological properties of monoclonal antibodies against glycoprotein D of herpes simplex virus and identification of amino acid substitutions that confer resistance to neutralization. Journal of General Virology 67, 1001-1013.[CrossRef]
    [Google Scholar]
  26. Montgomery, R. I., Warner, M. S., Lum, B. J. & Spear, P. G. ( 1996; ). Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87, 427-436.[CrossRef]
    [Google Scholar]
  27. Morgan, C., Rose, H. M. & Mednis, B. ( 1968; ). Electron microscopy of herpes simplex virus. I. Entry. Journal of Virology 2, 507-516.
    [Google Scholar]
  28. Muggeridge, M. I., Wu, T.-T., Johnson, D. C., Glorioso, J. C., Eisenberg, R. J. & Cohen, G. H. ( 1990; ). Antigenic and functional analysis of a neutralization site of HSV-1 glycoprotein D. Virology 174, 375-387.[CrossRef]
    [Google Scholar]
  29. Nicola, A. V., Willis, S. H., Naidoo, N. N., Eisenberg, R. J. & Cohen, G. H. ( 1996; ). Structure-function analysis of soluble forms of herpes simplex virus glycoprotein D. Journal of Virology 70, 3815-3822.
    [Google Scholar]
  30. Norton, D. D., Dwyer, D. S. & Muggeridge, M. I. ( 1998; ). Use of a neural network secondary structure prediction to define targets for mutagenesis of herpes simplex virus glycoprotein B. Virus Research 55, 37-48.[CrossRef]
    [Google Scholar]
  31. Novotny, M. J., Parish, M. L. & Spear, P. G. ( 1996; ). Variability of herpes simplex virus 1 gL and anti-gL antibodies that inhibit cell fusion but not viral infectivity. Virology 221, 1-13.[CrossRef]
    [Google Scholar]
  32. Para, M. F., Parish, M. L., Noble, A. G. & Spear, P. G. ( 1985; ). Potent neutralizing activity associated with anti-glycoprotein D specificity among monoclonal antibodies selected for binding to herpes simplex virions. Journal of Virology 55, 483-488.
    [Google Scholar]
  33. Pereira, L., Ali, M., Kousoulas, K., Huo, B. & Banks, T. ( 1989; ). Domain structure of herpes simplex virus 1 glycoprotein B: neutralizing epitopes map in regions of continuous and discontinuous residues. Virology 172, 11-24.[CrossRef]
    [Google Scholar]
  34. 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]
  35. Scott, T. F. M. & McLeod, D. L. ( 1959; ). Cellular responses to infection with strains of herpes simplex virus. Annals of the New York Academy of Sciences 81, 118-128.
    [Google Scholar]
  36. Spear, P. G. ( 1993; ). Membrane fusion induced by herpes simplex virus. In Viral Fusion Mechanisms, pp. 201-232. Edited by J. Bentz. Boca Raton, FL: CRC Press.
  37. Terry-Allison, T., Montgomery, R. I., Whitbeck, J. C., Xu, R., Cohen, G. H., Eisenberg, R. J. & Spear, P. G. ( 1998; ). HveA (herpesvirus entry mediator A), a coreceptor for herpes simplex virus entry, also participates in virus-induced cell fusion. Journal of Virology 72, 5802-5810.
    [Google Scholar]
  38. Turner, A., Bruun, B., Minson, T. & Browne, H. ( 1998; ). Glycoproteins gB, gD, and gHgL of herpes simplex virus type 1 are necessary and sufficient to mediate membrane fusion in a Cos cell transfection system. Journal of Virology 72, 873-875.
    [Google Scholar]
  39. Walev, I., Weise, K. & Falke, D. ( 1991; ). Differentiation of herpes simplex virus-induced fusion from without and fusion from within by cyclosporin A and compound 48/80. Journal of General Virology 72, 1377-1382.[CrossRef]
    [Google Scholar]
  40. Walev, I., Lingen, M., Lazzaro, M., Weise, K. & Falke, D. ( 1994; ). Cyclosporin A resistance of herpes simplex virus-induced ‘fusion from within’ as a phenotypical marker of mutations in the syn 3 locus of the glycoprotein B gene. Virus Genes 8, 83-86.[CrossRef]
    [Google Scholar]
  41. Warner, M. S., Geraghty, R. J., Martinez, W. M., Montgomery, R. I., Whitbeck, J. C., Xu, R., Eisenberg, R. J., Cohen, G. H. & Spear, P. G. ( 1998; ). A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus. Virology 246, 179-189.[CrossRef]
    [Google Scholar]
  42. Wheeler, C. E.Jr ( 1964; ). Biologic comparison of a syncytial and a small giant cell-forming strain of herpes simplex. Journal of Immunology 93, 749-756.
    [Google Scholar]
  43. Willis, S. H., Rux, A. H., Peng, C., Whitbeck, J. C., Nicola, A. V., Lou, H., Hou, W., Salvador, L., Eisenberg, R. J. & Cohen, G. H. ( 1998; ). Examination of the kinetics of herpes simplex virus glycoprotein D binding to the herpesvirus entry mediator, using surface plasmon resonance. Journal of Virology 72, 5937-5947.
    [Google Scholar]
  44. Wittels, M. & Spear, P. G. ( 1990; ). Penetration of cells by herpes simplex virus does not require a low pH-dependent endocytic pathway. Virus Research 18, 271-290.
    [Google Scholar]
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