The Role of Herpes Simplex Virus Glycoproteins in Immune Evasion

  • G. Dubin
  • N. O. Fishman
  • R. J. Eisenberg
  • G. H. Cohen
  • H. M. Friedman
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 179)


Viruses have evolved mechanisms that favor their own survival by modifying the effectiveness of the host immune response. Although viral strategies for immune evasion are varied, many members of the herpesvirus family encode proteins that have immunoregulatory functions. Human cytomegalovirus (CMV) encodes a protein that shares homology with the heavy chain of the major histocompatibility complex class I molecule (Beck and Barrell 1988). This protein interacts with β 2-microglobulin and may interfere with cytotoxic T cell recognition of infected cells (Browne et al. 1990). BCRF1, a protein encoded by Epstein-Barr virus (EBV), is a homologue of interleukin-10 and inhibits synthesis of cytokines by activated T helper cells (Hsu et al. 1990).


Herpes Simplex Virus Type Immune Evasion Alternative Complement Pathway Herpes Simplex Virus Glycoprotein Primary Herpes Simplex Virus Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adler R, Glorioso J, Cossman J, Levine M (1978) Possible role of Fc receptors on cells infected and transformed by herpesvirus: escape from immune cytolysis. Infect Immun 21: 442–447PubMedGoogle Scholar
  2. Baucke RB, Spear PG (1979) Membrane proteins specified by herpes simplex viruses. V. Identification of an Fc-binding glycoprotein. J Virol 32: 779–789PubMedGoogle Scholar
  3. Beck S, Barreil BG (1988) Human cytomegalovirus encodes a glycoprotein homologous to MHC class I antigens. Nature 331: 269–272PubMedCrossRefGoogle Scholar
  4. Bell S, Cranage M, Borysiewicz L, Minson T (1990) Induction of immunoglobulin G Fc receptors by recombinant vaccinia viruses expressing glycoproteins E and I of herpes simplex virus type 1. J Virol 64: 2181–2186Google Scholar
  5. Browne, H, Smith G, Beck S, Minson T (1990) A complex between the MHC class I homologue encoded by human cytomegalovirus and β2 microglobulin. Nature 347: 770–772PubMedCrossRefGoogle Scholar
  6. Cines DB, Lyss AP, Bina M, Corkey R, Kefalides NA, Friedman HM (1982) Fc and C3 receptors induced by herpes simplex virus on cultured human endothelial cells. J Clin Invest 69: 123–128PubMedCrossRefGoogle Scholar
  7. Costa J, Rabson AS, Yee C, Tralka TS (1977) Immunoglobulin binding to herpes virus-induced Fc receptors inhibits virus growth. Nature 269: 251–252PubMedCrossRefGoogle Scholar
  8. Costa J, Yee C, Nakamura Y, Rabson A (1978) Characteristics of the Fc receptor induced by herpes simplex virus. Intervirology 10: 32–39PubMedCrossRefGoogle Scholar
  9. Dierich MP, Huemer HP, Prodinger WM (1989) C3 binding proteins of foreign origin. In: Lambris JD (ed) The third component of complement: chemistry and biology. Springer, Berlin Heidelberg New York, pp 163–178 (Current topics in microbiology and immunology, vol 153)Google Scholar
  10. Dix RD, McKendall RR, Baringer JR (1983) Comparative neurovirulence to herpes simplex virus type 1 strains after peripheral or intracerebral inoculation of BALB/c mice. Infect Immun 40:103–112PubMedGoogle Scholar
  11. Dowler K, Veltri R (1984) In vitro neutralization of HSV-2: inhibition of binding of normal and purified Fc to virion Fc receptor (FcR). J Med Virol 13: 251–259PubMedCrossRefGoogle Scholar
  12. Dubin G, Frank I, Friedman HM (1990) Herpes simplex virus type 1 encodes two Fc receptors which have different binding characteristics for monomeric immunoglobulin G (IgG) and IgG complexes. J Virol 64: 2725–2731PubMedGoogle Scholar
  13. Dubin G, Socolof E, Frank I, Friedman HM (1991) The herpes simplex virus type 1 Fc receptor protects infected cells from antibody dependent cellular cytotoxicity. J Virol 65: 7046–7050PubMedGoogle Scholar
  14. Eisenberg RJ, Ponce de Leon M, Friedman HM, Fries LF, Frank MM, Hastings JC, Cohen GH (1987) Complement component C3b binds directly to purified glycoprotein C of herpes simplex virus types 1 and 2. Microb Pathog 3: 423–435PubMedCrossRefGoogle Scholar
  15. Frank I, Friedman HM (1989) A novel function of the herpes simplex virus type 1 Fc receptor: participation in bipolar bridging of antiviral immunoglobulin G. J Virol 63: 4479–4488PubMedGoogle Scholar
  16. Friedman HM, Cohen GH, Eisenberg RJ, Seidel CA, Cines DB (1984) Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells. Nature 309: 633–635PubMedCrossRefGoogle Scholar
  17. Friedman HM, Glorioso JC, Cohen GH, Hastings JC, Harris SL, Eisenberg RJ (1986) Binding of complement component C3b to glycoprotein C of herpes simplex virus type 1: mapping of gC-binding sites and demonstration of conserved C3b binding in low-passage clinical isolates. J Virol 60: 470–475PubMedGoogle Scholar
  18. Fries LF, Friedman HM, Cohen GH, Eisenberg RJ, Hammer CH, Frank MM (1986) Glycoprotein C of herpes simplex virus 1 is an inhibitor of the complement cascade. J Immunol 137: 1636–1641PubMedGoogle Scholar
  19. Frink RJ, Eisenberg R, Cohen G, Wagner EK (1983) Detailed analysis of the portion of the herpes simplex virus type 1 genome encoding glycoprotein C. J Virol 45: 634–647PubMedGoogle Scholar
  20. Hanke T, Graham FL, Lulitanand V, Johnson DC (1990) Herpes simplex virus IgG Fc receptors induced using recombinant adenovirus vectors expressing glycoproteins E and I. Virol 177: 437–444Google Scholar
  21. Harris SL, Frank I, Yee A, Cohen GH, Eisenberg RJ, Friedman HM (1990) Glycoprotein C of herpes simplex virus type 1 prevents complement-mediated cell lysis and virus neutralization. J Infect Dis 162: 331–337PubMedCrossRefGoogle Scholar
  22. Hidaka Y, Sakai Y, Yasushi T, Mori R (1991) Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells. J Gen Virol 72: 915–921PubMedCrossRefGoogle Scholar
  23. Hsu D-H, Malefyt RDW, Fiorentino DF, Dang M-H, Vieira P, DeVries J, Spits H, Mosmann TR, Moore KW (1990) Expression of interleukin-10 activity by Epstein-Barr virus protein BCRFI. Science 250: 830–832PubMedCrossRefGoogle Scholar
  24. Johansson PJH, Blomberg J (1990) Characterization of herpes simplex virus type 1-induced Fc receptor in its interaction with rabbit immunoglobulin G (IgG). Acta Pathol Microbiol Immunol Scand 98: 685–694CrossRefGoogle Scholar
  25. Johansson PJH, Kjellen L (1988) Inhibition of herpes simplex virus growth caused by preparations of animal immunoglobulins is not dependent on Fc-Fc receptor interactions. Intervirol 29: 334–338Google Scholar
  26. Johansson PJH, Hallberg T, Oxelius V-A, Grubb A, Blomberg J (1984) Human immunoglobulin class and subclass specificity of Fc receptors induced by herpes simplex virus type 1. J Virol 50: 796–804PubMedGoogle Scholar
  27. Johansson PJH, Myhre EB, Blomberg J (1985) Specificity of Fc receptors induced by herpes simplex virus type 1: comparison of immunoglobulin G from different animal species. J Virol 56: 489–494PubMedGoogle Scholar
  28. Johansson PJH, Schroder AK, Nardella FA, Mannik M, Christensen P (1986) Interaction between herpes simplex type 1-induced Fc receptor and human and rabbit immunoglobulin G (IgG) domains. Immunology 58: 251–255PubMedGoogle Scholar
  29. Jennings SR, Lippe PA, Pauza KJ, Spear PG, Pereira L, Tevethia SS (1987) Kenetics of expression of herpes simplex virus type 1-specific glycoprotein species on the surfaces of infected murine, simian, and human cells: flow cytometric analysis. J Virol 61:104–112PubMedGoogle Scholar
  30. Johnson DC, Feenstra V (1987) Identification of a novel herpes simplex virus type 1-induced glycoprotein which complexes with gE and binds immunoglobulin. J Virol 61: 2208–2216PubMedGoogle Scholar
  31. Johnson DC, McDermott MR, Chrisp C, Glorioso JC (1986) Pathogenicity in mice of herpes simplex virus type 2 mutants unable to express glycoprotein C. J Virol 58: 36–42PubMedGoogle Scholar
  32. Johnson DC, Frame MC, Ligas MW, Cross AM, Stow ND (1988) Herpes simplex virus immunoglobulin G Fc receptor activity depends on a complex of two viral glycoproteins, gE and gl. J Virol 62: 1347–1354PubMedGoogle Scholar
  33. Keller R, Peitchel R, Goldman JN (1976) An IgG Fc receptor induced in cytomegalovirus-infected human fibroblasts. J Immunol 116: 772–777PubMedGoogle Scholar
  34. Kubota Y, Gaither TA, Cason J, O’Shea JJ, Lawley TJ (1987) Characterization of the C3 receptor induced by herpes simplex virus type I infection of human epidermal, endothelial, and A431 cells. J Immunol 138: 1137–1142PubMedGoogle Scholar
  35. Lambris JD (1988) The multifunctional role of C3, the third component of complement. Immunol Today 9: 387–393PubMedCrossRefGoogle Scholar
  36. Lehner T, Wilton JMA, Shillitoe EJ (1979) Immunological basis for latency, recurrences, and putative oncogenicity of herpes simplex virus. Lancet ii: 60–62Google Scholar
  37. Litwin V, Sandor M, Grose C (1990) Cell surface expression of the varicella zoster virus glycoproteins and Fc receptor. Virology 178: 263–272PubMedCrossRefGoogle Scholar
  38. McGeoch DJ, Dolan A, Donald S, Rixon FJ (1985) Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. J Mol Biol 181: 1–13PubMedCrossRefGoogle Scholar
  39. McGeoch DJ, Dalrymple MA, Davison AJ, Dolan A, Frame MC, McNab D, Perry LJ, Scott JE, Taylor P (1988) The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 69: 1531–1574PubMedCrossRefGoogle Scholar
  40. McNearney TA, Odell C, Holers M, Spear PG, Atkinson JP (1987) Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity. J Exp Med 166:1525–1535PubMedCrossRefGoogle Scholar
  41. McTaggart SP, Burns WH, White DO, Jackson DC (1978) Fc receptors induced by herpes simplex virus. I. Biologic and biochemical properties. J Immunol 121: 726–730PubMedGoogle Scholar
  42. Mold C, Bradt BM, Nemerow GR, Cooper NR (1988) Epstein-Barr virus regulates activation and processing of the third component of complement. J Exp Med 168: 949–969PubMedCrossRefGoogle Scholar
  43. Nakamura Y, Costa J, Tralka TS, Yee CJ, Rabson AS (1978) Properties of the cell surface Fc-receptor induced by herpes simplex virus. J Immunol 121: 1128–1131PubMedGoogle Scholar
  44. Para MF, Baucke RB, Spear PG (1980) 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 34:512–520PubMedGoogle Scholar
  45. Para MF, Goldstein L, Spear PG (1982) Similarities and differences in the Fc-binding glycoprotein (gE) of herpes simplex virus types 1 and 2 and tentative mapping of the viral gene for this glycoprotein. J Virol 41: 137–144PubMedGoogle Scholar
  46. Seidel-Dugan C, Ponce de Leon M, Friedman HM, Fries LF, Frank MM, Cohen GH, Eisenberg RJ (1988) C3b receptor activity on transfected cells expressing glycoprotein C of herpes simplex virus types 1 and 2. J Virol 62: 4027–4026PubMedGoogle Scholar
  47. Seidel-Dugan C, Ponce de Leon M, Friedman HM, Eisenberg RJ, Cohen GH (1990) Identification of C3b-binding regions on herpes simplex virus type 2 glycoprotein C. J Virol 64: 1897–1906PubMedGoogle Scholar
  48. Sjöblom I, Lundström M, Sjögren-Jansson E, Glorioso JC, Jeansson S, Olofsson S (1987) Demonstration of highly carbohydrate dependent epitopes in the herpes simplex virus type 1-specified glycoprotein C. J Gen Virol 68: 545–554PubMedCrossRefGoogle Scholar
  49. Smiley ML, Friedman HM (1985) Binding of complement component C3b to glycoprotein C is modulated by sialic acid on herpes simplex virus type 1-infected cells. J Virol 55: 857–861PubMedGoogle Scholar
  50. Sunstrum JC, Chrisp CE, Levine M, Glorioso JC (1988) Pathogenicity of glycoprotein C negative mutants of herpes simplex virus type 1 for the mouse central nervous system. Virus Res 11:17–32PubMedCrossRefGoogle Scholar
  51. Tal-Singer R, Seidel-Duagn C, Fries LF, Huemer HP, Eisenberg RJ, Cohen GH, Friedman HM (1991) Herpes simplex virus glycoprotein C is a receptor for complement component iC3b. J Infect Dis 164: 750–753PubMedCrossRefGoogle Scholar
  52. Unkeless JC (1989) Function and heterogeneity of human Fc receptors for immunoglobulin G. J Clin Invest 83: 355–361PubMedCrossRefGoogle Scholar
  53. Watkins JF (1964) Adsorption of sensitized sheep erythrocytes to HeLa cells infected with herpes simplex virus. Nature 202:1364–1365PubMedCrossRefGoogle Scholar
  54. Westmoreland D, Watkins JF (1974) The IgG receptor induced by herpes simplex virus: studies using radioiodinated IgG. J Gen Virol 24:167–178PubMedCrossRefGoogle Scholar
  55. Yasuda J, Milgrom (1968) Hemadsorption by herpes simplex-infected cell cultures. Int Arch Allergy 33: 151–170PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin, Heidelberg 1992

Authors and Affiliations

  • G. Dubin
    • 1
  • N. O. Fishman
    • 1
  • R. J. Eisenberg
    • 3
    • 4
  • G. H. Cohen
    • 2
    • 3
  • H. M. Friedman
    • 1
    • 5
  1. 1.Infectious Diseases Section, Department of Medicine, School of MedicineUniversity of PennsylvaniaUSA
  2. 2.Department of MicrobiologyUniversity of PennsylvaniaUSA
  3. 3.Center for Oral Health Research, School of Dental MedicineUniversity of PennsylvaniaUSA
  4. 4.Department of Pathobiology, School of Veterinary MedicineUniversity of PennsylvaniaUSA
  5. 5.Department of Pathology and Laboratory MedicineChildren’s Hospital of PhiladelphiaPhiladelphiaUSA

Personalised recommendations