Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Jul;69(7):4556–4563. doi: 10.1128/jvi.69.7.4556-4563.1995

Herpes simplex virus glycoprotein K is known to influence fusion of infected cells, yet is not on the cell surface.

L Hutchinson 1, C Roop-Beauchamp 1, D C Johnson 1
PMCID: PMC189205  PMID: 7769723

Abstract

Syncytial mutants of herpes simplex virus (HSV) cause extensive fusion of cultured cells, whereas wild-type HSV primarily causes cell rounding and aggregation. A large fraction of syncytial viruses contain mutations in the UL53 gene, which encodes glycoprotein K (gK). Previously, we demonstrated that wild-type and syncytial forms of gK are expressed at similar levels and possess identical electrophoretic mobilities. Using immunofluorescence, we show that gK is not transported to the surfaces of cells infected with either wild-type or syncytial HSV. Instead, gK accumulates in the perinuclear and nuclear membranes of cells. This finding is in contrast to the behavior of all other HSV glycoproteins described to date, which reach the cell surface. When gK was expressed in the absence of other HSV proteins, using a recombinant adenovirus vector, a similar perinuclear and nuclear pattern was observed. In addition, gK remained sensitive to endoglycosidase H, consistent with the hypothesis that gK does not reach the Golgi apparatus and is retained in the endoplasmic reticulum and nuclear envelope. Therefore, although gK mutations promote fusion between the surface membranes of HSV-infected cells, the glycoprotein does not reach the plasma membrane and, thus, must influence fusion indirectly.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Baines J. D., Roizman B. The UL10 gene of herpes simplex virus 1 encodes a novel viral glycoprotein, gM, which is present in the virion and in the plasma membrane of infected cells. J Virol. 1993 Mar;67(3):1441–1452. doi: 10.1128/jvi.67.3.1441-1452.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baines J. D., Ward P. L., Campadelli-Fiume G., Roizman B. The UL20 gene of herpes simplex virus 1 encodes a function necessary for viral egress. J Virol. 1991 Dec;65(12):6414–6424. doi: 10.1128/jvi.65.12.6414-6424.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bond V. C., Person S. Fine structure physical map locations of alterations that affect cell fusion in herpes simplex virus type 1. Virology. 1984 Jan 30;132(2):368–376. doi: 10.1016/0042-6822(84)90042-4. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Bzik D. J., Person S. Dependence of herpes simplex virus type 1-induced cell fusion on cell type. Virology. 1981 Apr 15;110(1):35–42. doi: 10.1016/0042-6822(81)90005-2. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Cohen G. H., Katze M., Hydrean-Stern C., Eisenberg R. J. Type-common CP-1 antigen of herpes simplex virus is associated with a 59,000-molecular-weight envelope glycoprotein. J Virol. 1978 Jul;27(1):172–181. doi: 10.1128/jvi.27.1.172-181.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
  10. DebRoy C. Nucleotide sequence of the herpes simplex virus type-2 syn gene that causes cell fusion. Gene. 1990 Apr 16;88(2):275–277. doi: 10.1016/0378-1119(90)90043-q. [DOI] [PubMed] [Google Scholar]
  11. Debroy C., Pederson N., Person S. Nucleotide sequence of a herpes simplex virus type 1 gene that causes cell fusion. Virology. 1985 Aug;145(1):36–48. doi: 10.1016/0042-6822(85)90199-0. [DOI] [PubMed] [Google Scholar]
  12. Dingwell K. S., Brunetti C. R., Hendricks R. L., Tang Q., Tang M., Rainbow A. J., Johnson D. C. Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. J Virol. 1994 Feb;68(2):834–845. doi: 10.1128/jvi.68.2.834-845.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Forrester A. J., Sullivan V., Simmons A., Blacklaws B. A., Smith G. L., Nash A. A., Minson A. C. Induction of protective immunity with antibody to herpes simplex virus type 1 glycoprotein H (gH) and analysis of the immune response to gH expressed in recombinant vaccinia virus. J Gen Virol. 1991 Feb;72(Pt 2):369–375. doi: 10.1099/0022-1317-72-2-369. [DOI] [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. Ghiasi H., Slanina S., Nesburn A. B., Wechsler S. L. Characterization of baculovirus-expressed herpes simplex virus type 1 glycoprotein K. J Virol. 1994 Apr;68(4):2347–2354. doi: 10.1128/jvi.68.4.2347-2354.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gompels U., Minson A. The properties and sequence of glycoprotein H of herpes simplex virus type 1. Virology. 1986 Sep;153(2):230–247. doi: 10.1016/0042-6822(86)90026-7. [DOI] [PubMed] [Google Scholar]
  18. HOGGAN M. D., ROIZMAN B. The isolation and properties of a variant of Herpes simplex producing multinucleated giant cells in monolayer cultures in the presence of antibody. Am J Hyg. 1959 Sep;70:208–219. doi: 10.1093/oxfordjournals.aje.a120071. [DOI] [PubMed] [Google Scholar]
  19. Haj-Ahmad Y., Graham F. L. Development of a helper-independent human adenovirus vector and its use in the transfer of the herpes simplex virus thymidine kinase gene. J Virol. 1986 Jan;57(1):267–274. doi: 10.1128/jvi.57.1.267-274.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hanke T., Graham F. L., Lulitanond V., Johnson D. C. Herpes simplex virus IgG Fc receptors induced using recombinant adenovirus vectors expressing glycoproteins E and I. Virology. 1990 Aug;177(2):437–444. doi: 10.1016/0042-6822(90)90507-n. [DOI] [PubMed] [Google Scholar]
  21. Hutchinson L., Browne H., Wargent V., Davis-Poynter N., Primorac S., Goldsmith K., Minson A. C., Johnson D. C. 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. 1992 Apr;66(4):2240–2250. doi: 10.1128/jvi.66.4.2240-2250.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hutchinson L., Goldsmith K., Snoddy D., Ghosh H., Graham F. L., Johnson D. C. Identification and characterization of a novel herpes simplex virus glycoprotein, gK, involved in cell fusion. J Virol. 1992 Sep;66(9):5603–5609. doi: 10.1128/jvi.66.9.5603-5609.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hutchinson L., Graham F. L., Cai W., Debroy C., Person S., Johnson D. C. Herpes simplex virus (HSV) glycoproteins B and K inhibit cell fusion induced by HSV syncytial mutants. Virology. 1993 Oct;196(2):514–531. doi: 10.1006/viro.1993.1507. [DOI] [PubMed] [Google Scholar]
  24. Johnson D. C., Feenstra V. Identification of a novel herpes simplex virus type 1-induced glycoprotein which complexes with gE and binds immunoglobulin. J Virol. 1987 Jul;61(7):2208–2216. doi: 10.1128/jvi.61.7.2208-2216.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Johnson D. C., Frame M. C., Ligas M. W., Cross A. M., Stow N. D. Herpes simplex virus immunoglobulin G Fc receptor activity depends on a complex of two viral glycoproteins, gE and gI. J Virol. 1988 Apr;62(4):1347–1354. doi: 10.1128/jvi.62.4.1347-1354.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Johnson D. C., Ghosh-Choudhury G., Smiley J. R., Fallis L., Graham F. L. Abundant expression of herpes simplex virus glycoprotein gB using an adenovirus vector. Virology. 1988 May;164(1):1–14. doi: 10.1016/0042-6822(88)90613-7. [DOI] [PubMed] [Google Scholar]
  27. Johnson D. C., Smiley J. R. Intracellular transport of herpes simplex virus gD occurs more rapidly in uninfected cells than in infected cells. J Virol. 1985 Jun;54(3):682–689. doi: 10.1128/jvi.54.3.682-689.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Johnson D. C., Spear P. G. Monensin inhibits the processing of herpes simplex virus glycoproteins, their transport to the cell surface, and the egress of virions from infected cells. J Virol. 1982 Sep;43(3):1102–1112. doi: 10.1128/jvi.43.3.1102-1112.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Johnson D. C., Spear P. G. O-linked oligosaccharides are acquired by herpes simplex virus glycoproteins in the Golgi apparatus. Cell. 1983 Mar;32(3):987–997. doi: 10.1016/0092-8674(83)90083-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kornfeld R., Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54:631–664. doi: 10.1146/annurev.bi.54.070185.003215. [DOI] [PubMed] [Google Scholar]
  31. Lee G. T., Spear P. G. Viral and cellular factors that influence cell fusion induced by herpes simplex virus. Virology. 1980 Dec;107(2):402–414. doi: 10.1016/0042-6822(80)90307-4. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. MacLean C. A., Efstathiou S., Elliott M. L., Jamieson F. E., McGeoch D. J. Investigation of herpes simplex virus type 1 genes encoding multiply inserted membrane proteins. J Gen Virol. 1991 Apr;72(Pt 4):897–906. doi: 10.1099/0022-1317-72-4-897. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. McGeoch D. J., Cunningham C., McIntyre G., Dolan A. 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. 1991 Dec;72(Pt 12):3057–3075. doi: 10.1099/0022-1317-72-12-3057. [DOI] [PubMed] [Google Scholar]
  36. Person S., Knowles R. W., Read G. S., Warner S. C., Bond V. C. Kinetics of cell fusion induced by a syncytia-producing mutant of herpes simplex virus type I. J Virol. 1975 Jan;17(1):183–190. doi: 10.1128/jvi.17.1.183-190.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pogue-Geile K. L., Lee G. T., Shapira S. K., Spear P. G. Fine mapping of mutations in the fusion-inducing MP strain of herpes simplex virus type 1. Virology. 1984 Jul 15;136(1):100–109. doi: 10.1016/0042-6822(84)90251-4. [DOI] [PubMed] [Google Scholar]
  38. Pogue-Geile K. L., Spear P. G. The single base pair substitution responsible for the Syn phenotype of herpes simplex virus type 1, strain MP. Virology. 1987 Mar;157(1):67–74. doi: 10.1016/0042-6822(87)90314-x. [DOI] [PubMed] [Google Scholar]
  39. Ramaswamy R., Holland T. C. In vitro characterization of the HSV-1 UL53 gene product. Virology. 1992 Feb;186(2):579–587. doi: 10.1016/0042-6822(92)90024-j. [DOI] [PubMed] [Google Scholar]
  40. Read G. S., Person S., Keller P. M. Genetic studies of cell fusion induced by herpes simplex virus type 1. J Virol. 1980 Jul;35(1):105–113. doi: 10.1128/jvi.35.1.105-113.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Roberts S. R., Ponce de Leon M., Cohen G. H., Eisenberg R. J. Analysis of the intracellular maturation of the herpes simplex virus type 1 glycoprotein gH in infected and transfected cells. Virology. 1991 Oct;184(2):609–624. doi: 10.1016/0042-6822(91)90431-a. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Ruyechan W. T., Morse L. S., Knipe D. M., Roizman B. Molecular genetics of herpes simplex virus. II. Mapping of the major viral glycoproteins and of the genetic loci specifying the social behavior of infected cells. J Virol. 1979 Feb;29(2):677–697. doi: 10.1128/jvi.29.2.677-697.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schutze M. P., Peterson P. A., Jackson M. R. An N-terminal double-arginine motif maintains type II membrane proteins in the endoplasmic reticulum. EMBO J. 1994 Apr 1;13(7):1696–1705. doi: 10.1002/j.1460-2075.1994.tb06434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sodora D. L., Cohen G. H., Eisenberg R. J. Influence of asparagine-linked oligosaccharides on antigenicity, processing, and cell surface expression of herpes simplex virus type 1 glycoprotein D. J Virol. 1989 Dec;63(12):5184–5193. doi: 10.1128/jvi.63.12.5184-5193.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sullivan V., Smith G. L. Expression and characterization of herpes simplex virus type 1 (HSV-1) glycoprotein G (gG) by recombinant vaccinia virus: neutralization of HSV-1 infectivity with anti-gG antibody. J Gen Virol. 1987 Oct;68(Pt 10):2587–2598. doi: 10.1099/0022-1317-68-10-2587. [DOI] [PubMed] [Google Scholar]
  47. Telford E. A., Watson M. S., McBride K., Davison A. J. The DNA sequence of equine herpesvirus-1. Virology. 1992 Jul;189(1):304–316. doi: 10.1016/0042-6822(92)90706-u. [DOI] [PubMed] [Google Scholar]
  48. Wenske E. A., Bratton M. W., Courtney R. J. Endo-beta-N-acetylglucosaminidase H sensitivity of precursors to herpes simplex virus type 1 glycoproteins gB and gC. J Virol. 1982 Oct;44(1):241–248. doi: 10.1128/jvi.44.1.241-248.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. York I. A., Roop C., Andrews D. W., Riddell S. R., Graham F. L., Johnson D. C. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell. 1994 May 20;77(4):525–535. doi: 10.1016/0092-8674(94)90215-1. [DOI] [PubMed] [Google Scholar]
  50. Zhao Y., Holden V. R., Harty R. N., O'Callaghan D. J. Identification and transcriptional analyses of the UL3 and UL4 genes of equine herpesvirus 1, homologs of the ICP27 and glycoprotein K genes of herpes simplex virus. J Virol. 1992 Sep;66(9):5363–5372. doi: 10.1128/jvi.66.9.5363-5372.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES