1887

Abstract

Human herpesviruses enter cells by fusion of their own membrane with a cellular membrane through the concerted action of multiple viral proteins and cellular receptors. Two conserved viral glycoproteins, gB and gH, are required for herpes simplex virus type 1 (HSV-1)-mediated membrane fusion, but little is known of how these proteins cooperate during entry. Both glycoproteins were shown to contain heptad repeat (HR) sequences predicted to form -helical coiled coils, and the inhibitory activity against infection of four sets of synthetic peptides corresponding to HR1 and HR2 of gB and gH was tested. The interactions between these HR peptides were also investigated by circular dichroism, native polyacrylamide-gel electrophoresis and size exclusion high-performance liquid chromatography. gH coiled-coil peptides were more effective than gB coiled-coils peptides in inhibiting virus infectivity. The peptides did not impair fusion when added to cells immediately after infection. In contrast, inhibition of infection was observed, albeit to various extents, when peptides were added to virus before or during inoculation. The results of biophysical analyses were indicative of the existence of an interaction between HR1 and HR2 of gH and suggest that the HRs of gB and gH do not interact with each other.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81794-0
2006-05-01
2024-12-12
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/5/1085.html?itemId=/content/journal/jgv/10.1099/vir.0.81794-0&mimeType=html&fmt=ahah

References

  1. Baker K. A., Dutch R. E., Lamb R. A., Jardetzky T. S. 1999; Structural basis for paramyxovirus-mediated membrane fusion. Mol Cell 3:309–319 [CrossRef]
    [Google Scholar]
  2. Blumenthal R., Clague M. J., Durell S. R., Epand R. M. 2003; Membrane fusion. Chem Rev 103:53–69 [CrossRef]
    [Google Scholar]
  3. Bullough P. A., Hughson F. M., Skehel J. J., Wiley D. C. 1994; Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371:37–43 [CrossRef]
    [Google Scholar]
  4. Caffrey M., Cai M., Kaufman J., Stahl S. J., Wingfield P. T., Covell D. G., Gronenenborn A. M., Clore G. M. 1998; Three-dimensional structure of the 44 kDa ectodomain of SIV gp41. EMBO J 17:4572–4584 [CrossRef]
    [Google Scholar]
  5. Chambers P., Pringle C. R., Easton A. J. 1990; Heptad repeat sequences are located adjacent to hydrophobic regions in several types of virus fusion glycoproteins. J Gen Virol 71:3075–3080 [CrossRef]
    [Google Scholar]
  6. Chan D. C., Kim P. S. 1998; HIV entry and its inhibition. Cell 93:681–684 [CrossRef]
    [Google Scholar]
  7. Chen J., Skehel J. J., Wiley D. C. 1999; N- and C-terminal residues combine in the fusion-pH influenza hemagglutinin HA2 subunit to form an N cap that terminates the triple-stranded coiled coil. Proc Natl Acad Sci U S A 96:8967–8972 [CrossRef]
    [Google Scholar]
  8. 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. J Virol 72:9992–10002
    [Google Scholar]
  9. Cocchi F., Fusco D., Menotti L., Gianni T., Eisenberg R. J., Cohen G. H., Campadelli-Fiume G. 2004; The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry. Proc Natl Acad Sci U S A 101:7445–7450 [CrossRef]
    [Google Scholar]
  10. Dimitrov D. S. 2004; Virus entry: molecular mechanisms and biomedical applications. Nat Rev Microbiol 2:109–122 [CrossRef]
    [Google Scholar]
  11. Earp L. J., Delos S. E., Park H. E., White J. M. 2005; The many mechanisms of viral membrane fusion proteins. Curr Top Microbiol Immunol 285:25–66
    [Google Scholar]
  12. Eckert D. M., Kim P. S. 2001; Mechanism of viral membrane fusion and its inhibition. Annu Rev Biochem 70:777–810 [CrossRef]
    [Google Scholar]
  13. Fass D., Harrison S. C., Kim P. S. 1996; Retrovirus envelope domain at 1·7 angstrom resolution. Nat Struct Biol 3:465–469 [CrossRef]
    [Google Scholar]
  14. 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. J Virol 66:341–348
    [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. Heldwein K., Lou H., Whitbeck J. C., Cohen G., Eisenberg R. J., Harrison S. 2005 International Herpesvirus Workshop; Turku, Finland:
  20. Hernandez L. D., Hoffman L. R., Wolfsberg T. G., White J. M. 1996; Virus-cell and cell-cell fusion. Annu Rev Cell Dev Biol 12:627–661 [CrossRef]
    [Google Scholar]
  21. Ingallinella P., Bianchi E., Finotto M., Cantoni G., Eckert D. M., Supekar V. M., Bruckmann C., Carfi A., Pessi A. 2004; Structural characterization of the fusion-active complex of severe acute respiratory syndrome (SARS) coronavirus. Proc Natl Acad Sci U S A 101:8709–8714 [CrossRef]
    [Google Scholar]
  22. Jahn R., Lang T., Sudhof T. C. 2003; Membrane fusion. Cell 112:519–533 [CrossRef]
    [Google Scholar]
  23. Jardetzky T. S., Lamb R. A. 2004; Virology: a class act. Nature 427:307–308 [CrossRef]
    [Google Scholar]
  24. Joshi S. B., Dutch R. E., Lamb R. A. 1998; A core trimer of the paramyxovirus fusion protein: parallels to influenza virus hemagglutinin and HIV-1 gp41. Virology 248:20–34 [CrossRef]
    [Google Scholar]
  25. Kilby J. M., Hopkins S., Venetta T. M. & 12 other authors 1998; Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 4:1302–1307 [CrossRef]
    [Google Scholar]
  26. Kobe B., Center R. J., Kemp B. E., Poumbourios P. 1999; Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins. Proc Natl Acad Sci U S A 96:4319–4324 [CrossRef]
    [Google Scholar]
  27. Lambert D. M., Barney S., Lambert A. L. 7 other authors 1996; Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc Natl Acad Sci U S A 93:2186–2191 [CrossRef]
    [Google Scholar]
  28. Liu S., Zhao Q., Jiang S. 2003; Determination of the HIV-1 gp41 fusogenic core conformation modelled by synthetic peptides: applicable for identification of HIV-1 fusion inhibitors. Peptides 24:1303–1313 [CrossRef]
    [Google Scholar]
  29. Liu S., Lu H., Niu J., Xu Y., Wu S., Jiang S. 2005; Different from the HIV fusion inhibitor C34, the anti-HIV drug Fuzeon (T-20) inhibits HIV-1 entry by targeting multiple sites in gp41 and gp120. J Biol Chem 280:11259–11273 [CrossRef]
    [Google Scholar]
  30. Lopez M., Cocchi F., Menotti L., Avitabile E., Dubreuil P., Campadelli-Fiume G. 2000; Nectin2alpha (PRR2alpha or HveB) and nectin2delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D. J Virol 74:1267–1274 [CrossRef]
    [Google Scholar]
  31. 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]
  32. Lupas A., Van Dyke M., Stock J. 1991; Predicting coiled coils from protein sequences. Science 252:1162–1164 [CrossRef]
    [Google Scholar]
  33. Malashkevich V. N., Chan D. C., Chutkowski C. T., Kim P. S. 1998; Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides. Proc Natl Acad Sci U S A 95:9134–9139 [CrossRef]
    [Google Scholar]
  34. Malashkevich V. N., Schneider B. J., McNally M. L., Milhollen M. A., Pang J. X., Kim P. S. 1999; Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-Å resolution. Proc Natl Acad Sci U S A 96:2662–2667 [CrossRef]
    [Google Scholar]
  35. Malashkevich V. N., Singh M., Kim P. S. 2001; The trimer-of-hairpins motif in membrane fusion: visna virus. Proc Natl Acad Sci U S A 98:8502–8506 [CrossRef]
    [Google Scholar]
  36. Melikyan G. B., Markosyan R. M., Hemmati H., Delmedico M. K., Lambert D. M., Cohen F. S. 2000; Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J Cell Biol 151:413–423 [CrossRef]
    [Google Scholar]
  37. Mettenleiter T. C. 2002a; Brief overview on cellular virus receptors. Virus Res 82:3–8
    [Google Scholar]
  38. Mettenleiter T. C. 2002b; Herpesvirus assembly and egress. J Virol 76:1537–1547 [CrossRef]
    [Google Scholar]
  39. 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]
  40. Okazaki K., Kida H. 2004; A synthetic peptide from a heptad repeat region of herpesvirus glycoprotein B inhibits virus replication. J Gen Virol 85:2131–2137 [CrossRef]
    [Google Scholar]
  41. Rapaport D., Ovadia M., Shai Y. 1995; A synthetic peptide corresponding to a conserved heptad repeat domain is a potent inhibitor of Sendai virus-cell fusion: an emerging similarity with functional domains of other viruses. EMBO J 14:5524–5531
    [Google Scholar]
  42. Russell C. J., Jardetzky T. S., Lamb R. A. 2001; Membrane fusion machines of paramyxoviruses: capture of intermediates of fusion. EMBO J 20:4024–4034 [CrossRef]
    [Google Scholar]
  43. Skehel J. J., Wiley D. C. 1998; Coiled coils in both intracellular vesicle and viral membrane fusion. Cell 95:871–874 [CrossRef]
    [Google Scholar]
  44. Spear P. G. 2004; Herpes simplex virus: receptors and ligands for cell entry. Cell Microbiol 6:401–410 [CrossRef]
    [Google Scholar]
  45. Spear P. G., Longnecker R. 2003; Herpesvirus entry: an update. J Virol 77:10179–10185 [CrossRef]
    [Google Scholar]
  46. 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]
  47. 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]
  48. Weissenhorn W., Dessen A., Harrison S. C., Skehel J. J., Wiley D. C. 1997; Atomic structure of the ectodomain from HIV-1 gp41. Nature 387:426–430 [CrossRef]
    [Google Scholar]
  49. Weissenhorn W., Calder L. J., Wharton S. A., Skehel J. J., Wiley D. C. 1998; The central structural feature of the membrane fusion protein subunit from the Ebola virus glycoprotein is a long triple-stranded coiled coil. Proc Natl Acad Sci U S A 95:6032–6036 [CrossRef]
    [Google Scholar]
  50. Weissenhorn W., Dessen A., Calder L. J., Harrison S. C., Skehel J. J., Wiley D. C. 1999; Structural basis for membrane fusion by enveloped viruses. Mol Membr Biol 16:3–9 [CrossRef]
    [Google Scholar]
  51. Wild T. F., Buckland R. 1997; Inhibition of measles virus infection and fusion with peptides corresponding to the leucine zipper region of the fusion protein. J Gen Virol 78:107–111
    [Google Scholar]
  52. Wild C. T., Shugars D. C., Greenwell T. K., McDanal C. B., Matthews T. J. 1994; Peptides corresponding to a predictive α -helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc Natl Acad Sci U S A 91:9770–9774 [CrossRef]
    [Google Scholar]
  53. Yuan K., Yi L., Chen J. & 15 other authors 2004; Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein. Biochem Biophys Res Commun 319:746–752 [CrossRef]
    [Google Scholar]
  54. Zhao X., Singh M., Malashkevich V. N., Kim P. S. 2000; Structural characterization of the human respiratory syncytial virus fusion protein core. Proc Natl Acad Sci U S A 97:14172–14177 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.81794-0
Loading
/content/journal/jgv/10.1099/vir.0.81794-0
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