1887

Journal of General Virology header logo

Volume 89, Issue 6

Glycoprotein B switches conformation during murid herpesvirus 4 entry Free

Abstract

Herpesviruses are ancient pathogens that infect all vertebrates. The most conserved component of their entry machinery is glycoprotein B (gB), yet how gB functions is unclear. A striking feature of the murid herpesvirus 4 (MuHV-4) gB is its resistance to neutralization. Here, we show by direct visualization of infected cells that the MuHV-4 gB changes its conformation between extracellular virions and those in late endosomes, where capsids are released. Specifically, epitopes on its N-terminal cell-binding domain become inaccessible, whilst non-N-terminal epitopes are revealed, consistent with structural changes reported for the vesicular stomatitis virus glycoprotein G. Inhibitors of endosomal acidification blocked the gB conformation switch. They also blocked capsid release and the establishment of infection, implying that the gB switch is a key step in entry. Neutralizing antibodies could only partially inhibit the switch. Their need to engage a less vulnerable, upstream form of gB, because its fusion form is revealed only in endosomes, helps to explain why gB-directed MuHV-4 neutralization is so difficult.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83519-0
2008-06-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/6/1352.html?itemId=/content/journal/jgv/10.1099/vir.0.83519-0&mimeType=html&fmt=ahah

References

  1. Adler H., Messerle M., Wagner M., Koszinowski U. H. 2000; Cloning and mutagenesis of the murine gammaherpesvirus 68 genome as an infectious bacterial artificial chromosome. J Virol 74:6964–6974 [CrossRef]
     [Google Scholar]
  2. Akula S. M., Pramod N. P., Wang F. Z., Chandran B. 2002; Integrin α 3 β 1 (CD 49c/29) is a cellular receptor for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. Cell 108:407–419 [CrossRef]
     [Google Scholar]
  3. Akula S. M., Naranatt P. P., Walia N. S., Wang F. Z., Fegley B., Chandran B. 2003; Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) infection of human fibroblast cells occurs through endocytosis. J Virol 77:7978–7990 [CrossRef]
     [Google Scholar]
  4. Balachandran N., Bacchetti S., Rawls W. E. 1982; Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2. Infect Immun 37:1132–1137
     [Google Scholar]
  5. Bender F. C., Samanta M., Heldwein E. E., de Leon M. P., Bilman E., Lou H., Whitbeck J. C., Eisenberg R. J., Cohen G. H. 2007; Antigenic and mutational analyses of herpes simplex virus glycoprotein B reveal four functional regions. J Virol 81:3827–3841 [CrossRef]
     [Google Scholar]
  6. Browne H., Bruun B., Minson T. 2001; Plasma membrane requirements for cell fusion induced by herpes simplex virus type 1 glycoproteins gB, gD, gH and gL. J Gen Virol 82:1419–1422
     [Google Scholar]
  7. Chen B., Vogan E. M., Gong H., Skehel J. J., Wiley D. C., Harrison S. C. 2005; Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433:834–841 [CrossRef]
     [Google Scholar]
  8. Clement C., Tiwari V., Scanlan P. M., Valyi-Nagy T., Yue B. Y., Shukla D. 2006; A novel role for phagocytosis-like uptake in herpes simplex virus entry. J Cell Biol 174:1009–1021 [CrossRef]
     [Google Scholar]
  9. Compton T., Nepomuceno R. R., Nowlin D. M. 1992; Human cytomegalovirus penetrates host cells by pH-independent fusion at the cell surface. Virology 191:387–395 [CrossRef]
     [Google Scholar]
  10. de Lima B. D., May J. S., Stevenson P. G. 2004; Murine gammaherpesvirus 68 lacking gp150 shows defective virion release but establishes normal latency in vivo. J Virol 78:5103–5112 [CrossRef]
     [Google Scholar]
  11. Demaurex N., Furuya W., D'Souza S., Bonifacino J. S., Grinstein S. 1998; Mechanism of acidification of the trans -Golgi network (TGN). In situ measurements of pH using retrieval of TGN38 and furin from the cell surface. J Biol Chem 273:2044–2051 [CrossRef]
     [Google Scholar]
  12. Dingwell K. S., Brunetti C. R., Hendricks R. L., Tang Q., Tang M., Rainbow A. J., Johnson D. C. 1994; Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. J Virol 68:834–845
     [Google Scholar]
  13. Fusco D., Forghieri C., Campadelli-Fiume G. 2005; The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with the gD N terminus and is displaced by soluble forms of viral receptors. Proc Natl Acad Sci U S A 102:9323–9328 [CrossRef]
     [Google Scholar]
  14. Gill M. B., Gillet L., Colaco S., May J. S., de Lima B. D., Stevenson P. G. 2006; Murine gammaherpesvirus-68 glycoprotein H-glycoprotein L complex is a major target for neutralizing monoclonal antibodies. J Gen Virol 87:1465–1475 [CrossRef]
     [Google Scholar]
  15. Gillet L., Stevenson P. G. 2007a; Evidence for a multi-protein gamma-2-herpesvirus entry complex. J Virol 81:13082–13091 [CrossRef]
     [Google Scholar]
  16. Gillet L., Stevenson P. G. 2007b; Antibody evasion by the N terminus of murid herpesvirus-4 glycoprotein B. EMBO J 26:5131–5142 [CrossRef]
     [Google Scholar]
  17. Gillet L., Gill M. B., Colaco S., Smith C. M., Stevenson P. G. 2006; Murine gammaherpesvirus-68 glycoprotein B presents a difficult neutralization target to monoclonal antibodies derived from infected mice. J Gen Virol 87:3515–3527 [CrossRef]
     [Google Scholar]
  18. Gillet L., May J. S., Colaco S., Stevenson P. G. 2007a; The murine gammaherpesvirus-68 gp150 acts as an immunogenic decoy to limit virion neutralization. PLoS ONE 2:e705 [CrossRef]
     [Google Scholar]
  19. Gillet L., May J. S., Stevenson P. G. 2007b; Post-exposure vaccination improves gammaherpesvirus neutralization. PLoS ONE 2:e899 [CrossRef]
     [Google Scholar]
  20. Gillet L., Adler H., Stevenson P. G. 2007c; Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. PLoS ONE 2:e347 [CrossRef]
     [Google Scholar]
  21. Gillet L., May J. S., Colaco S., Stevenson P. G. 2007d; Glycoprotein L disruption reveals two functional forms of the murine gammaherpesvirus 68 glycoprotein H. J Virol 81:280–291 [CrossRef]
     [Google Scholar]
  22. Heldwein E. E., Lou H., Bender F. C., Cohen G. H., Eisenberg R. J., Harrison S. C. 2006; Crystal structure of glycoprotein B from herpes simplex virus 1. Science 313:217–220 [CrossRef]
     [Google Scholar]
  23. Holloway S. A., Studdert M. J., Drummer H. E. 1998; Characterization of glycoprotein B of the gammaherpesvirus equine herpesvirus-2. J Gen Virol 79:1619–1629
     [Google Scholar]
  24. Klasse P. J., Sattentau Q. J. 2002; Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J Gen Virol 83:2091–2108
     [Google Scholar]
  25. Knossow M., Skehel J. J. 2006; Variation and infectivity neutralization in influenza. Immunology 119:1–7 [CrossRef]
     [Google Scholar]
  26. Kohl S., Loo L. S., Schmalstieg F. S., Anderson D. C. 1986; The>genetic deficiency of leukocyte surface glycoprotein Mac-1, LFA-1, p150,95 in humans is associated with defective antibody-dependent cellular cytotoxicity in vitro and defective protection against herpes simplex virus infection in vivo. J Immunol 137:1688–1694
     [Google Scholar]
  27. Köhler G., Milstein C. 1975; Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497 [CrossRef]
     [Google Scholar]
  28. Krummenacher C., Supekar V. M., Whitbeck J. C., Lazear E., Connolly S. A., Eisenberg R. J., Cohen G. H., Wiley D. C., Carfi A. 2005; Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. EMBO J 24:4144–4153 [CrossRef]
     [Google Scholar]
  29. Lopes F. B., Colaco S., May J. S., Stevenson P. G. 2004; Characterization of murine gammaherpesvirus 68 glycoprotein B. J Virol 78:13370–13375 [CrossRef]
     [Google Scholar]
  30. Marsh M., Schmid S., Kern H., Harms E., Male P., Mellman I., Helenius A. 1987; Rapid analytical and preparative isolation of functional endosomes by free flow electrophoresis. J Cell Biol 104:875–886 [CrossRef]
     [Google Scholar]
  31. May J. S., Coleman H. M., Boname J. M., Stevenson P. G. 2005a; The murine gamma-herpesvirus-68 ORF28 encodes a non-essential virion glycoprotein. J Gen Virol 86:919–928 [CrossRef]
     [Google Scholar]
  32. May J. S., Colaco S., Stevenson P. G. 2005b; Glycoprotein M is an essential lytic replication protein of the murine gammaherpesvirus 68. J Virol 79:3459–3467 [CrossRef]
     [Google Scholar]
  33. Nagashunmugam T., Lubinski J., Wang L., Goldstein L. T., Weeks B. S., Sundaresan P., Kang E. H., Dubin G., Friedman H. M. 1998; In vivo immune evasion mediated by the herpes simplex virus type 1 immunoglobulin G Fc receptor. J Virol 72:5351–5359
     [Google Scholar]
  34. Ohlin M., Sundqvist V. A., Mach M., Wahren B., Borrebaeck C. A. 1993; Fine specificity of the human immune response to the major neutralization epitopes expressed on cytomegalovirus gp58/116 (gB), as determined with human monoclonal antibodies. J Virol 67:703–710
     [Google Scholar]
  35. Okazaki K., Fujii S., Takada A., Kida H. 2006; The amino-terminal residue of glycoprotein B is critical for neutralization of bovine herpesvirus 1. Virus Res 115:105–111 [CrossRef]
     [Google Scholar]
  36. Peeters B., Pol J., Gielkens A., Moormann R. 1993; Envelope glycoprotein gp50 of pseudorabies virus is essential for virus entry but is not required for viral spread in mice. J Virol 67:170–177
     [Google Scholar]
  37. Pertel P. E. 2002; Human herpesvirus 8 glycoprotein B (gB), gH, and gL can mediate cell fusion. J Virol 76:4390–4400 [CrossRef]
     [Google Scholar]
  38. Rector J. T., Lausch R. N., Oakes J. E. 1982; Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection. Infect Immun 38:168–174
     [Google Scholar]
  39. Roche S., Bressanelli S., Rey F. A., Gaudin Y. 2006; Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science 313:187–191 [CrossRef]
     [Google Scholar]
  40. Roche S., Rey F. A., Gaudin Y., Bressanelli S. 2007; Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G. Science 315:843–848 [CrossRef]
     [Google Scholar]
  41. Rosa G. T., Gillet L., Smith C. M., de Lima B. D., Stevenson P. G. 2007; IgG Fc receptors provide an alternative infection route for murine gamma-herpesvirus-68. PLoS ONE 2:e560 [CrossRef]
     [Google Scholar]
  42. Roth M. G., Compans R. W. 1980; Antibody-resistant spread of vesicular stomatitis virus infection in cell lines of epithelial origin. J Virol 35:547–550
     [Google Scholar]
  43. Ryckman B. J., Jarvis M. A., Drummond D. D., Nelson J. A., Johnson D. C. 2006; Human cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion. J Virol 80:710–722 [CrossRef]
     [Google Scholar]
  44. Shannon-Lowe C. D., Neuhierl B., Baldwin G., Rickinson A. B., Delecluse H. J. 2006; Resting B cells as a transfer vehicle for Epstein-Barr virus infection of epithelial cells. Proc Natl Acad Sci U S A 103:7065–7070 [CrossRef]
     [Google Scholar]
  45. Spear P. G., Longnecker R. 2003; Herpesvirus entry: an update. J Virol 77:10179–10185 [CrossRef]
     [Google Scholar]
  46. Speckner A., Glykofrydes D., Ohlin M., Mach M. 1999; Antigenic domain 1 of human cytomegalovirus glycoprotein B induces a multitude of different antibodies which, when combined, results in incomplete virus neutralization. J Gen Virol 80:2183–2191
     [Google Scholar]
  47. 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. J Virol 72:873–875
     [Google Scholar]
  48. Xu J., Lyons P. A., Carter M. D., Booth T. W., Davis-Poynter N. J., Shellam G. R., Scalzo A. A. 1996; Assessment of antigenicity and genetic variation of glycoprotein B of murine cytomegalovirus. J Gen Virol 77:49–59 [CrossRef]
     [Google Scholar]
  49. Yewdell J. W., Hill A. B. 2002; Viral interference with antigen presentation. Nat Immunol 3:1019–1025 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83519-0
Loading
Glycoprotein B switches conformation during murid herpesvirus 4 entry
J. Gen. Virol. 89, 1352 (2008); https://doi.org/10.1099/vir.0.83519-0
/content/journal/jgv/10.1099/vir.0.83519-0
/content/journal/jgv/10.1099/vir.0.83519-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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