Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Oct;71(10):8024–8028. doi: 10.1128/jvi.71.10.8024-8028.1997

Partial resistance to gD-mediated interference conferred by mutations affecting herpes simplex virus type 1 gC and gK.

P E Pertel 1, P G Spear 1
PMCID: PMC192166  PMID: 9311899

Abstract

Cells expressing herpes simplex virus (HSV) gD can be resistant to HSV entry as a result of gD-mediated interference. HSV strains differ in sensitivity to this interference, which blocks viral penetration but not binding. Previous studies have shown that mutations or variations in virion-associated gD can confer resistance to gD-mediated interference. Here we show that HSV-1 mutants selected for enhanced ability to bind and penetrate in the presence of inhibitory concentrations of heparin were partially resistant to gD-mediated interference. The resistance was largely due to the presence of two mutations: one in gC (the major heparin-binding glycoprotein) resulting in the absence of gC expression and the other in gK resulting in a syncytial phenotype. The results imply that heparin selected for mutants with altered postbinding requirements for entry. Resistance to gD-mediated interference conferred by mutations affecting gC and gK has not been previously described.

Full Text

The Full Text of this article is available as a PDF (226.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Addison C., Rixon F. J., Palfreyman J. W., O'Hara M., Preston V. G. Characterisation of a herpes simplex virus type 1 mutant which has a temperature-sensitive defect in penetration of cells and assembly of capsids. Virology. 1984 Oct 30;138(2):246–259. doi: 10.1016/0042-6822(84)90349-0. [DOI] [PubMed] [Google Scholar]
  2. Batterson W., Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol. 1983 May;46(2):371–377. doi: 10.1128/jvi.46.2.371-377.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brunetti C. R., Burke R. L., Hoflack B., Ludwig T., Dingwell K. S., Johnson D. C. Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission. J Virol. 1995 Jun;69(6):3517–3528. doi: 10.1128/jvi.69.6.3517-3528.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brunetti C. R., Burke R. L., Kornfeld S., Gregory W., Masiarz F. R., Dingwell K. S., Johnson D. C. Herpes simplex virus glycoprotein D acquires mannose 6-phosphate residues and binds to mannose 6-phosphate receptors. J Biol Chem. 1994 Jun 24;269(25):17067–17074. [PubMed] [Google Scholar]
  5. Cai W. H., Gu B., Person S. Role of glycoprotein B of herpes simplex virus type 1 in viral entry and cell fusion. J Virol. 1988 Aug;62(8):2596–2604. doi: 10.1128/jvi.62.8.2596-2604.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Campadelli-Fiume G., Arsenakis M., Farabegoli F., Roizman B. Entry of herpes simplex virus 1 in BJ cells that constitutively express viral glycoprotein D is by endocytosis and results in degradation of the virus. J Virol. 1988 Jan;62(1):159–167. doi: 10.1128/jvi.62.1.159-167.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Campadelli-Fiume G., Qi S., Avitabile E., Foà-Tomasi L., Brandimarti R., Roizman B. Glycoprotein D of herpes simplex virus encodes a domain which precludes penetration of cells expressing the glycoprotein by superinfecting herpes simplex virus. J Virol. 1990 Dec;64(12):6070–6079. doi: 10.1128/jvi.64.12.6070-6079.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Campbell M. E., Palfreyman J. W., Preston C. M. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J Mol Biol. 1984 Nov 25;180(1):1–19. doi: 10.1016/0022-2836(84)90427-3. [DOI] [PubMed] [Google Scholar]
  9. Cassai E. N., Sarmiento M., Spear P. G. Comparison of the virion proteins specified by herpes simplex virus types 1 and 2. J Virol. 1975 Nov;16(5):1327–1331. doi: 10.1128/jvi.16.5.1327-1331.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chase C. C., Carter-Allen K., Lohff C., Letchworth G. J., 3rd Bovine cells expressing bovine herpesvirus 1 (BHV-1) glycoprotein IV resist infection by BHV-1, herpes simplex virus, and pseudorabies virus. J Virol. 1990 Oct;64(10):4866–4872. doi: 10.1128/jvi.64.10.4866-4872.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chase C. C., Lohff C., Letchworth G. J., 3rd Resistance and susceptibility of bovine cells expressing herpesviral glycoprotein D homologs to herpesviral infections. Virology. 1993 May;194(1):365–369. doi: 10.1006/viro.1993.1269. [DOI] [PubMed] [Google Scholar]
  12. Cohen G. H., Ponce de Leon M., Diggelmann H., Lawrence W. C., Vernon S. K., Eisenberg R. J. Structural analysis of the capsid polypeptides of herpes simplex virus types 1 and 2. J Virol. 1980 May;34(2):521–531. doi: 10.1128/jvi.34.2.521-531.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dean H. J., Terhune S. S., Shieh M. T., Susmarski N., Spear P. G. Single amino acid substitutions in gD of herpes simplex virus 1 confer resistance to gD-mediated interference and cause cell-type-dependent alterations in infectivity. Virology. 1994 Feb 15;199(1):67–80. doi: 10.1006/viro.1994.1098. [DOI] [PubMed] [Google Scholar]
  14. Dean H. J., Warner M. S., Terhune S. S., Johnson R. M., Spear P. G. Viral determinants of the variable sensitivity of herpes simplex virus strains to gD-mediated interference. J Virol. 1995 Aug;69(8):5171–5176. doi: 10.1128/jvi.69.8.5171-5176.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Forrester A., Farrell H., Wilkinson G., Kaye J., Davis-Poynter N., Minson T. Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. J Virol. 1992 Jan;66(1):341–348. doi: 10.1128/jvi.66.1.341-348.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fuller A. O., Lee W. C. Herpes simplex virus type 1 entry through a cascade of virus-cell interactions requires different roles of gD and gH in penetration. J Virol. 1992 Aug;66(8):5002–5012. doi: 10.1128/jvi.66.8.5002-5012.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fuller A. O., Spear P. G. Anti-glycoprotein D antibodies that permit adsorption but block infection by herpes simplex virus 1 prevent virion-cell fusion at the cell surface. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5454–5458. doi: 10.1073/pnas.84.15.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gruenheid S., Gatzke L., Meadows H., Tufaro F. Herpes simplex virus infection and propagation in a mouse L cell mutant lacking heparan sulfate proteoglycans. J Virol. 1993 Jan;67(1):93–100. doi: 10.1128/jvi.67.1.93-100.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Herold B. C., Visalli R. J., Susmarski N., Brandt C. R., Spear P. G. Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B. J Gen Virol. 1994 Jun;75(Pt 6):1211–1222. doi: 10.1099/0022-1317-75-6-1211. [DOI] [PubMed] [Google Scholar]
  20. Herold B. C., WuDunn D., Soltys N., Spear P. G. Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity. J Virol. 1991 Mar;65(3):1090–1098. doi: 10.1128/jvi.65.3.1090-1098.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Holland T. C., Sandri-Goldin R. M., Holland L. E., Marlin S. D., Levine M., Glorioso J. C. Physical mapping of the mutation in an antigenic variant of herpes simplex virus type 1 by use of an immunoreactive plaque assay. J Virol. 1983 May;46(2):649–652. doi: 10.1128/jvi.46.2.649-652.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Huang T., Campadelli-Fiume G. Anti-idiotypic antibodies mimicking glycoprotein D of herpes simplex virus identify a cellular protein required for virus spread from cell to cell and virus-induced polykaryocytosis. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1836–1840. doi: 10.1073/pnas.93.5.1836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Isola V. J., Eisenberg R. J., Siebert G. R., Heilman C. J., Wilcox W. C., Cohen G. H. Fine mapping of antigenic site II of herpes simplex virus glycoprotein D. J Virol. 1989 May;63(5):2325–2334. doi: 10.1128/jvi.63.5.2325-2334.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jackson R. L., Busch S. J., Cardin A. D. Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol Rev. 1991 Apr;71(2):481–539. doi: 10.1152/physrev.1991.71.2.481. [DOI] [PubMed] [Google Scholar]
  25. Johnson R. M., Spear P. G. Herpes simplex virus glycoprotein D mediates interference with herpes simplex virus infection. J Virol. 1989 Feb;63(2):819–827. doi: 10.1128/jvi.63.2.819-827.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Karger A., Mettenleiter T. C. Glycoproteins gIII and gp50 play dominant roles in the biphasic attachment of pseudorabies virus. Virology. 1993 Jun;194(2):654–664. doi: 10.1006/viro.1993.1305. [DOI] [PubMed] [Google Scholar]
  27. Lee W. C., Fuller A. O. Herpes simplex virus type 1 and pseudorabies virus bind to a common saturable receptor on Vero cells that is not heparan sulfate. J Virol. 1993 Sep;67(9):5088–5097. doi: 10.1128/jvi.67.9.5088-5097.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ligas M. W., Johnson D. C. A herpes simplex virus mutant in which glycoprotein D sequences are replaced by beta-galactosidase sequences binds to but is unable to penetrate into cells. J Virol. 1988 May;62(5):1486–1494. doi: 10.1128/jvi.62.5.1486-1494.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. MUNK K., DONNER D. CYTOPATHISCHER EFFEKT UND PLAQUE-MORPHOLOGIE VERSCHIEDENER HERPES-SIMPLEX-VIRUSSTAEMME. Arch Gesamte Virusforsch. 1963 Aug 26;13:529–540. [PubMed] [Google Scholar]
  30. Manservigi R., Spear P. G., Buchan A. Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3913–3917. doi: 10.1073/pnas.74.9.3913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Minson A. C., Hodgman T. C., Digard P., Hancock D. C., Bell S. E., Buckmaster E. A. 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. J Gen Virol. 1986 Jun;67(Pt 6):1001–1013. doi: 10.1099/0022-1317-67-6-1001. [DOI] [PubMed] [Google Scholar]
  32. Montgomery R. I., Warner M. S., Lum B. J., Spear P. G. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell. 1996 Nov 1;87(3):427–436. doi: 10.1016/s0092-8674(00)81363-x. [DOI] [PubMed] [Google Scholar]
  33. Morgan C., Rose H. M., Mednis B. Electron microscopy of herpes simplex virus. I. Entry. J Virol. 1968 May;2(5):507–516. doi: 10.1128/jvi.2.5.507-516.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Munk K., Ludwig G. Properties of plaque variants of herpes virus hominis strains of genital origin. Arch Gesamte Virusforsch. 1972;37(4):308–315. doi: 10.1007/BF01241453. [DOI] [PubMed] [Google Scholar]
  35. Para M. F., Baucke R. B., Spear P. G. Immunoglobulin G(Fc)-binding receptors on virions of herpes simplex virus type 1 and transfer of these receptors to the cell surface by infection. J Virol. 1980 May;34(2):512–520. doi: 10.1128/jvi.34.2.512-520.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pertel P. E., Spear P. G. Modified entry and syncytium formation by herpes simplex virus type 1 mutants selected for resistance to heparin inhibition. Virology. 1996 Dec 1;226(1):22–33. doi: 10.1006/viro.1996.0624. [DOI] [PubMed] [Google Scholar]
  37. Petrovskis E. A., Meyer A. L., Post L. E. Reduced yield of infectious pseudorabies virus and herpes simplex virus from cell lines producing viral glycoprotein gp50. J Virol. 1988 Jun;62(6):2196–2199. doi: 10.1128/jvi.62.6.2196-2199.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Roop C., Hutchinson L., Johnson D. C. A mutant herpes simplex virus type 1 unable to express glycoprotein L cannot enter cells, and its particles lack glycoprotein H. J Virol. 1993 Apr;67(4):2285–2297. doi: 10.1128/jvi.67.4.2285-2297.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sarmiento M., Haffey M., Spear P. G. Membrane proteins specified by herpes simplex viruses. III. Role of glycoprotein VP7(B2) in virion infectivity. J Virol. 1979 Mar;29(3):1149–1158. doi: 10.1128/jvi.29.3.1149-1158.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shieh M. T., Spear P. G. Herpesvirus-induced cell fusion that is dependent on cell surface heparan sulfate or soluble heparin. J Virol. 1994 Feb;68(2):1224–1228. doi: 10.1128/jvi.68.2.1224-1228.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Shieh M. T., WuDunn D., Montgomery R. I., Esko J. D., Spear P. G. Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. J Cell Biol. 1992 Mar;116(5):1273–1281. doi: 10.1083/jcb.116.5.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. TAKEMOTO K. K., FABISCH P. INHIBITION OF HERPES VIRUS BY NATURAL AND SYNTHETIC ACID POLYSACCHARIDES. Proc Soc Exp Biol Med. 1964 May;116:140–144. doi: 10.3181/00379727-116-29183. [DOI] [PubMed] [Google Scholar]
  43. Tikoo S. K., Fitzpatrick D. R., Babiuk L. A., Zamb T. J. Molecular cloning, sequencing, and expression of functional bovine herpesvirus 1 glycoprotein gIV in transfected bovine cells. J Virol. 1990 Oct;64(10):5132–5142. doi: 10.1128/jvi.64.10.5132-5142.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. VAHERI A., CANTELL K. THE EFFECT OF HEPARIN ON HERPES SIMPLEX VIRUS. Virology. 1963 Dec;21:661–662. doi: 10.1016/0042-6822(63)90242-3. [DOI] [PubMed] [Google Scholar]
  45. Whitbeck J. C., Peng C., Lou H., Xu R., Willis S. H., Ponce de Leon M., Peng T., Nicola A. V., Montgomery R. I., Warner M. S. Glycoprotein D of herpes simplex virus (HSV) binds directly to HVEM, a member of the tumor necrosis factor receptor superfamily and a mediator of HSV entry. J Virol. 1997 Aug;71(8):6083–6093. doi: 10.1128/jvi.71.8.6083-6093.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wittels M., Spear P. G. Penetration of cells by herpes simplex virus does not require a low pH-dependent endocytic pathway. Virus Res. 1991 Mar;18(2-3):271–290. doi: 10.1016/0168-1702(91)90024-p. [DOI] [PubMed] [Google Scholar]
  47. WuDunn D., Spear P. G. Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol. 1989 Jan;63(1):52–58. doi: 10.1128/jvi.63.1.52-58.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES