Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1989 Jan;63(1):52–58. doi: 10.1128/jvi.63.1.52-58.1989

Initial interaction of herpes simplex virus with cells is binding to heparan sulfate.

D WuDunn 1, P G Spear 1
PMCID: PMC247656  PMID: 2535752

Abstract

We have shown that cell surface heparan sulfate serves as the initial receptor for both serotypes of herpes simplex virus (HSV). We found that virions could bind to heparin, a related glycosaminoglycan, and that heparin blocked virus adsorption. Agents known to bind to cell surface heparan sulfate blocked viral adsorption and infection. Enzymatic digestion of cell surface heparan sulfate but not of dermatan sulfate or chondroitin sulfate concomitantly reduced the binding of virus to the cells and rendered the cells resistant to infection. Although cell surface heparan sulfate was required for infection by HSV types 1 and 2, the two serotypes may bind to heparan sulfate with different affinities or may recognize different structural features of heparan sulfate. Consistent with their broad host ranges, the two HSV serotypes use as primary receptors ubiquitous cell surface components known to participate in interactions with the extracellular matrix and with other cell surfaces.

Full text

PDF
52

Images in this article

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. Brown M. S., Deuel T. F., Basu S. K., Goldstein J. L. Inhibition of the binding of low-density lipoprotein to its cell surface receptor in human fibroblasts by positively charged proteins. J Supramol Struct. 1978;8(3):223–234. doi: 10.1002/jss.400080302. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Cai W. Z., Person S., Warner S. C., Zhou J. H., DeLuca N. A. Linker-insertion nonsense and restriction-site deletion mutations of the gB glycoprotein gene of herpes simplex virus type 1. J Virol. 1987 Mar;61(3):714–721. doi: 10.1128/jvi.61.3.714-721.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Cole G. J., Glaser L. A heparin-binding domain from N-CAM is involved in neural cell-substratum adhesion. J Cell Biol. 1986 Feb;102(2):403–412. doi: 10.1083/jcb.102.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cole G. J., Loewy A., Glaser L. Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules. Nature. 1986 Apr 3;320(6061):445–447. doi: 10.1038/320445a0. [DOI] [PubMed] [Google Scholar]
  9. Cole G. J., Schubert D., Glaser L. Cell-substratum adhesion in chick neural retina depends upon protein-heparan sulfate interactions. J Cell Biol. 1985 Apr;100(4):1192–1199. doi: 10.1083/jcb.100.4.1192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Desai P. J., Schaffer P. A., Minson A. C. Excretion of non-infectious virus particles lacking glycoprotein H by a temperature-sensitive mutant of herpes simplex virus type 1: evidence that gH is essential for virion infectivity. J Gen Virol. 1988 Jun;69(Pt 6):1147–1156. doi: 10.1099/0022-1317-69-6-1147. [DOI] [PubMed] [Google Scholar]
  11. Draper K. G., Costa R. H., Lee G. T., Spear P. G., Wagner E. K. Molecular basis of the glycoprotein-C-negative phenotype of herpes simplex virus type 1 macroplaque strain. J Virol. 1984 Sep;51(3):578–585. doi: 10.1128/jvi.51.3.578-585.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ejercito P. M., Kieff E. D., Roizman B. Characterization of herpes simplex virus strains differing in their effects on social behaviour of infected cells. J Gen Virol. 1968 May;2(3):357–364. doi: 10.1099/0022-1317-2-3-357. [DOI] [PubMed] [Google Scholar]
  13. Esko J. D., Stewart T. E., Taylor W. H. Animal cell mutants defective in glycosaminoglycan biosynthesis. Proc Natl Acad Sci U S A. 1985 May;82(10):3197–3201. doi: 10.1073/pnas.82.10.3197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Esko J. D., Weinke J. L., Taylor W. H., Ekborg G., Rodén L., Anantharamaiah G., Gawish A. Inhibition of chondroitin and heparan sulfate biosynthesis in Chinese hamster ovary cell mutants defective in galactosyltransferase I. J Biol Chem. 1987 Sep 5;262(25):12189–12195. [PubMed] [Google Scholar]
  15. 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]
  16. Gill P. J., Silbert C. K., Silbert J. E. Effects of heparan sulfate removal on attachment and reattachment of fibroblasts and endothelial cells. Biochemistry. 1986 Jan 28;25(2):405–410. doi: 10.1021/bi00350a020. [DOI] [PubMed] [Google Scholar]
  17. Goldstein J. L., Basu S. K., Brunschede G. Y., Brown M. S. Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. Cell. 1976 Jan;7(1):85–95. doi: 10.1016/0092-8674(76)90258-0. [DOI] [PubMed] [Google Scholar]
  18. Highlander S. L., Cai W. H., Person S., Levine M., Glorioso J. C. Monoclonal antibodies define a domain on herpes simplex virus glycoprotein B involved in virus penetration. J Virol. 1988 Jun;62(6):1881–1888. doi: 10.1128/jvi.62.6.1881-1888.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Highlander S. L., Sutherland S. L., Gage P. J., Johnson D. C., Levine M., Glorioso J. C. Neutralizing monoclonal antibodies specific for herpes simplex virus glycoprotein D inhibit virus penetration. J Virol. 1987 Nov;61(11):3356–3364. doi: 10.1128/jvi.61.11.3356-3364.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Homa F. L., Purifoy D. J., Glorioso J. C., Levine M. Molecular basis of the glycoprotein C-negative phenotypes of herpes simplex virus type 1 mutants selected with a virus-neutralizing monoclonal antibody. J Virol. 1986 May;58(2):281–289. doi: 10.1128/jvi.58.2.281-289.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hök M., Kjellén L., Johansson S. Cell-surface glycosaminoglycans. Annu Rev Biochem. 1984;53:847–869. doi: 10.1146/annurev.bi.53.070184.004215. [DOI] [PubMed] [Google Scholar]
  22. Kjellén L., Pettersson I., Hök M. Cell-surface heparan sulfate: an intercalated membrane proteoglycan. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5371–5375. doi: 10.1073/pnas.78.9.5371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Laterra J., Silbert J. E., Culp L. A. Cell surface heparan sulfate mediates some adhesive responses to glycosaminoglycan-binding matrices, including fibronectin. J Cell Biol. 1983 Jan;96(1):112–123. doi: 10.1083/jcb.96.1.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Little S. P., Jofre J. T., Courtney R. J., Schaffer P. A. A virion-associated glycoprotein essential for infectivity of herpes simplex virus type 1. Virology. 1981 Nov;115(1):149–160. doi: 10.1016/0042-6822(81)90097-0. [DOI] [PubMed] [Google Scholar]
  26. Longnecker R., Roizman B. Clustering of genes dispensable for growth in culture in the S component of the HSV-1 genome. Science. 1987 May 1;236(4801):573–576. doi: 10.1126/science.3033823. [DOI] [PubMed] [Google Scholar]
  27. Markwell M. A., Fredman P., Svennerholm L. Receptor ganglioside content of three hosts for Sendai virus. MDBK, HeLa, and MDCK cells. Biochim Biophys Acta. 1984 Aug 8;775(1):7–16. doi: 10.1016/0005-2736(84)90228-1. [DOI] [PubMed] [Google Scholar]
  28. Mitsuya H., Looney D. J., Kuno S., Ueno R., Wong-Staal F., Broder S. Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells. Science. 1988 Apr 29;240(4852):646–649. doi: 10.1126/science.2452480. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Nahmias A. J., Kibrick S. Inhibitory effect of heparin on herpes simplex virus. J Bacteriol. 1964 May;87(5):1060–1066. doi: 10.1128/jb.87.5.1060-1066.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Neidhardt H., Schröder C. H., Kaerner H. C. Herpes simplex virus type 1 glycoprotein E is not indispensable for viral infectivity. J Virol. 1987 Feb;61(2):600–603. doi: 10.1128/jvi.61.2.600-603.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Rapraeger A., Bernfield M. Cell surface proteoglycan of mammary epithelial cells. Protease releases a heparan sulfate-rich ectodomain from a putative membrane-anchored domain. J Biol Chem. 1985 Apr 10;260(7):4103–4109. [PubMed] [Google Scholar]
  34. 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]
  35. Spear P. G., Roizman B. Proteins specified by herpes simplex virus. V. Purification and structural proteins of the herpesvirion. J Virol. 1972 Jan;9(1):143–159. doi: 10.1128/jvi.9.1.143-159.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stannard L. M., Fuller A. O., Spear P. G. Herpes simplex virus glycoproteins associated with different morphological entities projecting from the virion envelope. J Gen Virol. 1987 Mar;68(Pt 3):715–725. doi: 10.1099/0022-1317-68-3-715. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Vahlne A., Svennerholm B., Lycke E. Evidence for herpes simplex virus type-selective receptors on cellular plasma membranes. J Gen Virol. 1979 Jul;44(1):217–225. doi: 10.1099/0022-1317-44-1-217. [DOI] [PubMed] [Google Scholar]
  39. Vahlne A., Svennerholm B., Sandberg M., Hamberger A., Lycke E. Differences in attachment between herpes simplex type 1 and type 2 viruses to neurons and glial cells. Infect Immun. 1980 Jun;28(3):675–680. doi: 10.1128/iai.28.3.675-680.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES