1887

Abstract

The herpes simplex virus type 1 (HSV-1) glycoproteins H (gH) and L (gL) form a heterodimer and efficient expression of gH at the virion or cell surface is dependent upon gL. Five carboxy-terminal deletion mutants of gL were created and their ability to interact with and mediate cell-surface expression of gH, to promote binding of gL-dependent anti-gH antibodies and to contribute to cell fusion was analysed. All of the gL mutants bound gH, but only two mutants, containing the amino-terminal 161 or 168 aa of gL, mediated cell-surface expression of gH, and only gL161 and gL168 functioned in cell fusion. The binding of gL to gH, therefore, was not sufficient to ensure gH cell-surface expression and it was not possible to separate the gH-trafficking role of gL from gL function in fusion. Co-expression of gH with any gL mutant conferred binding of the anti-gH mAbs 53S and LP11. If the acquisition of 53S and LP11 binding to gH reflects a gL-induced conformational change, such a change is not sufficient to mediate trafficking of the gH–gL heterodimer.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81563-0
2006-04-01
2024-10-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/4/759.html?itemId=/content/journal/jgv/10.1099/vir.0.81563-0&mimeType=html&fmt=ahah

References

  1. Buckmaster E. A., Cranage M. P., McLean C. S., Coombs R. R., Minson A. 1984; The use of monoclonal antibodies to differentiate isolates of herpes simplex types 1 and 2 by neutralisation and reverse passive haemagglutination tests. J Med Virol 13:193–202 [CrossRef]
    [Google Scholar]
  2. Cairns T. M., Milne R. S. B., Ponce-De-Leon M., Tobin D. K., Cohen G. H., Eisenberg R. J. 2003; Structure-function analysis of herpes simplex virus type 1 gD and gH-gL: clues from gDgH chimeras. J Virol 77:6731–6742 [CrossRef]
    [Google Scholar]
  3. Cairns T. M., Landsburg D. J., Whitbeck J. C., Eisenberg R. J., Cohen G. H. 2005; Contribution of cysteine residues to the structure and function of herpes simplex virus gH/gL. Virology 332:550–562 [CrossRef]
    [Google Scholar]
  4. Dubin G., Jiang H. 1995; Expression of herpes simplex virus type 1 glycoprotein L (gL) in transfected mammalian cells: evidence that gL is not independently anchored to cell membranes. J Virol 69:4564–4568
    [Google Scholar]
  5. Duus K. M., Grose C. 1996; Multiple regulatory effects of varicella-zoster virus (VZV) gL on trafficking patterns and fusogenic properties of VZV gH. J Virol 70:8961–8971
    [Google Scholar]
  6. Galdiero S., Falanga A., Vitiello M., Browne H., Pedone C., Galdiero M. 2005; Fusogenic domains in herpes simplex virus type 1 glycoprotein H. J Biol Chem 280:28632–28643 [CrossRef]
    [Google Scholar]
  7. Geraghty R. J., Jogger C. R., Spear P. G. 2000; Cellular expression of alphaherpesvirus gD interferes with entry of homologous and heterologous alphaherpesviruses by blocking access to a shared gD receptor. Virology 268:147–158 [CrossRef]
    [Google Scholar]
  8. Geraghty R. J., Fridberg A., Krummenacher C., Cohen G. H., Eisenberg R. J., Spear P. G. 2001; Use of chimeric nectin-1(HveC)-related receptors to demonstrate that ability to bind alphaherpesvirus gD is not necessarily sufficient for viral entry. Virology 285:366–375 [CrossRef]
    [Google Scholar]
  9. Gianni T., Martelli P. L., Casadio R., Campadelli-Fiume G. 2005a; The ectodomain of herpes simplex virus glycoprotein H contains a membrane α -helix with attributes of an internal fusion peptide, positionally conserved in the Herpesviridae family. J Virol 79:2931–2940 [CrossRef]
    [Google Scholar]
  10. Gianni T., Menotti L., Campadelli-Fiume G. 2005b; A heptad repeat in herpes simplex virus 1 gH, located downstream of the α -helix with attributes of a fusion peptide, is critical for virus entry and fusion. J Virol 79:7042–7049 [CrossRef]
    [Google Scholar]
  11. Gompels U., Minson A. 1986; The properties and sequence of glycoprotein H of herpes simplex virus type 1. Virology 153:230–247 [CrossRef]
    [Google Scholar]
  12. Gompels U. A., Minson A. C. 1989; Antigenic properties and cellular localization of herpes simplex virus glycoprotein H synthesized in a mammalian cell expression system. J Virol 63:4744–4755
    [Google Scholar]
  13. Gompels U. A., Carss A. L., Saxby C., Hancock D. C., Forrester A., Minson A. C. 1991; Characterization and sequence analyses of antibody-selected antigenic variants of herpes simplex virus show a conformationally complex epitope on glycoprotein H. J Virol 65:2393–2401
    [Google Scholar]
  14. 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. J Virol 66:2240–2250
    [Google Scholar]
  15. Jones N. A., Geraghty R. J. 2004; Fusion activity of lipid-anchored envelope glycoproteins of herpes simplex virus type 1. Virology 324:213–228 [CrossRef]
    [Google Scholar]
  16. Lopper M., Compton T. 2004; Coiled-coil domains in glycoproteins B and H are involved in human cytomegalovirus membrane fusion. J Virol 78:8333–8341 [CrossRef]
    [Google Scholar]
  17. McGeoch D. J., Cunningham C., McIntyre G., Dolan A. 1991; Comparative sequence analysis of the long repeat regions and adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2. J Gen Virol 72:3057–3075 [CrossRef]
    [Google Scholar]
  18. 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]
  19. Nussbaum O., Broder C. C., Berger E. A. 1994; Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J Virol 68:5411–5422
    [Google Scholar]
  20. Oka T., Ungar D., Hughson F. M., Krieger M. 2004; The COG and COPI complexes interact to control the abundance of GEARs, a subset of Golgi integral membrane proteins. Mol Biol Cell 15:2423–2435 [CrossRef]
    [Google Scholar]
  21. Peng T., Ponce de Leon M., Novotny M. J., Jiang H., Lambris J. D., Dubin G., Spear P. G., Cohen G. H., Eisenberg R. J. 1998; Structural and antigenic analysis of a truncated form of the herpes simplex virus glycoprotein gH-gL complex. J Virol 72:6092–6103
    [Google Scholar]
  22. Pertel P. E., Fridberg A., Parish M. L., Spear P. G. 2001; Cell fusion induced by herpes simplex virus glycoproteins gB, gD, and gH-gL requires a gD receptor but not necessarily heparan sulfate. Virology 279:313–324 [CrossRef]
    [Google Scholar]
  23. 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. J Virol 67:2285–2297
    [Google Scholar]
  24. Showalter S. D., Zweig M., Hampar B. 1981; Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP 4. Infect Immun 34:684–692
    [Google Scholar]
  25. Subramanian R. P., Dunn J. E., Geraghty R. J. 2005; The nectin-1 α transmembrane domain, but not the cytoplasmic tail, influences cell fusion induced by HSV-1 glycoproteins. Virology 339:176–191 [CrossRef]
    [Google Scholar]
  26. 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]
  27. Ungar D., Oka T., Brittle E. E., Vasile E., Lupashin V. V., Chatterton J. E., Heuser J. E., Krieger M., Waters M. G. 2002; Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function. J Cell Biol 157:405–415 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.81563-0
Loading
/content/journal/jgv/10.1099/vir.0.81563-0
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