The Analysis of Immunity to Specific Proteins of Herpes Simplex and Varicella Zoster Virus and Its Clinical Applications

  • Ann M. Arvin
  • Wayne M. Sullender
  • Francois Boucher
  • Pamela S. Diaz
  • Paul A. Hensleigh
  • Charles G. Prober
Conference paper


Herpes viral glycoproteins are considered likely to be important targets of virus-specific immunity because they are expressed on the membranes of infected cells and because monoclonal antibodies to the surface glycoproteins of human herpes viruses often have neutralizing activity (Corey and Spear, 1986; Friedrichs and Grose, 1984; Keller et al. 1984; Rasmussen et al. 1985). Recent studies in viral immunology also demonstrate a host response to the nonglycosylated, internal or nucleoproteins of several viruses (Townsend et al. 1984; Yewdell et al. 1986). The investigation of immunity to proteins of both herpes simplex virus (HSV) and varicella-zoster virus (VZV) has progressed over the past few years in parallel with the expansion of knowledge about the molecular virology of these herpes viruses. These advances have allowed the mapping of gene sequences for many of the major viral proteins and their expression in plasmids and by transfection of mammalian cells (Davison and Scott, 1986; Pachl et al. 1987). Similarities between HSV and VZV have been defined at the molecular level with the identification of homologies between several gene sequences and, in the case of the HSV gB and VZV gp II, the demonstration of antigenic crossreactivity.


Genital Herpes Geometric Mean Titer Immune Individual Neonatal Herpes Neonatal Herpes Simplex Virus 
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  1. Ashley R, J Benedetti, L Corey (1985) Humoral immune response to HSV-1 and HSV-12 viral proteins in patients with primary genital herpes. J Med Virol 17: 153–166.PubMedCrossRefGoogle Scholar
  2. Ashley R, GJ Mertz, L Corey (1987) Detection of asymptomatic herpes simplex virus infections after vaccination. J Virol 61: 264–268.PubMedGoogle Scholar
  3. Arvin AM, CM Koropchak, Wittek AE (1983) Immunologic evidence of reinfection with varicella-zoster virus. J Infect Dis 148: 200–205.PubMedCrossRefGoogle Scholar
  4. Arvin AM, E Kinney-Thomas, K Shriver, C Grose, CM Koropchak, E Scranton, AE Wittek, PS Diaz (1986a) Immunity to varicella-zoster viral glycoproteins, gp I (gp90/58) and gp III (gp118) and to a nonglycosylated protein, p 170. J Immunol 137: 1346–1351.PubMedGoogle Scholar
  5. Arvin AM, CM Koropchak, BRG Williams, FC Grumet, SKH Foung (1986b) Early immune response in healthy and immunocompromised subjects with primary varicella zoster virus infection. J Infect Dis 154: 422–429.PubMedCrossRefGoogle Scholar
  6. Arvin AM, PA Hensleigh, CG Prober, DS Au, LL Yasukawa, AE Wittek, PE Palumbo, SG Paryani, AS Yeager (1986c) Failure of antepartum maternal cultures to predict the infant’s risk of exposure to herpes simplex virus at delivery. N Engl J Med 315: 796–800.Google Scholar
  7. Arvin AM, SM Solem, CM Korpchak, E Kinney-Thomas, SG Paryani (1987) Humoral and cellular immunity to varicella-zoster virus glycoprotein gp I and to non-glycosylated protein, p 170, in the strain 2 guinea pig. J Gen Virol 68: 2449–2454.PubMedCrossRefGoogle Scholar
  8. Bernstein DI, MA Lovett, YJ Bryson (1984) Serologic analysis of first-episode non-primary genital herpes simplex virus infection. Presence of type 2 antibody in acute serum. Am J Med 77: 1055–1060.PubMedCrossRefGoogle Scholar
  9. Boucher FB, LL Yasukawa, DS Au, PA Hensleigh, AM Arvin, CG Prober (1988) Longitudinal study of herpes simplex type 2 (HSV-2) seroprevalence and seroconversion among pregnant women. Abstract, 28th Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles.Google Scholar
  10. Brown ZA, LA Vontver, J Benedetti, CW Critchlow, SJ Sells, S Berry, L Corey (1988) Effects on infants of a first episode of genital herpes during pregnancy. N Engl J Med 317: 1246–1251.CrossRefGoogle Scholar
  11. Brunell PA, C Geiser, Z Shehab, JE Wangh (1982) Administration of live varicella vaccine to children with leukemia. Lancet 2: 1069–1072.PubMedCrossRefGoogle Scholar
  12. Brunell PA, VM Novelli, PM Keller, RW Ellis (1987) Antibodies to the three major glycoproteins of varicella-zoster virus: Search for the relevant host immune response. J Infect Dis 156: 430–435.Google Scholar
  13. Corey L, HG Adams, ZA Brown, KK Holmes (1983) Genital herpes simplex virus infections. Clinical manifestations, course, and complications. Ann Intern Med 98: 958–972.Google Scholar
  14. Corey L, PG Spear (1986) Infections with herpes simplex viruses. N Engl J Med 314:686–691 and 749–757.Google Scholar
  15. Cremer NE, CK Cossen, GR Shell, L Pereira (1985) Antibody response to cytomegalovirus polypeptides captured by monoclonal antibodies on the solid phase in enzyme immunoassays. J Clin Microbiol 21: 517–521.PubMedGoogle Scholar
  16. Davison AJ, CM Edson, RW Ellis, B Forghani, D Gilden, C Grose, PM Keller, A Vafai, Z Wroblewska, K Yamanishi (1986) A new nomenclature for the glycoprotein genes of varicella-zoster virus and their glycosylated producers. J Virol 57: 1195–1197.PubMedGoogle Scholar
  17. Davison AJ, JE Scott (1986) The complete DNA sequence of varicella-zoster virus. J Gen Virol 67: 1759–1816.PubMedCrossRefGoogle Scholar
  18. Diaz PS, S Smith, E Hunter, AM Arvin (1988) Immunity to whole varicella-zoster virus antigen, glycoprotein I and p 170 in relation to the immunization regimen with live attenuated varicella vaccine. Submitted.Google Scholar
  19. Friedrichs WE, C Grose (1984) Glycoprotein gp 118 of varicella-zoster virus: purification by serial affinity chromatography. J Virol 49: 992–996.PubMedGoogle Scholar
  20. Gershon AA, SP Steinberg, L Gelb, G Galasso, W Borkowsky, P LaRussa, A Ferrara (1984) Live attenuated varicella vaccine: Efficacy for children with leukemia in remission. JAMA 252: 355–362.Google Scholar
  21. Gershon AA, SP Steinberg, P LaRussa, A Ferrara, M Hammerschlag, L Gelb, and the NIAID varicella vaccine collaborative study group (1988) Immunization of healthy adults with live attenuated varicella vaccine. J Infect Dis, in press.Google Scholar
  22. Grose C (1987) Varicella-zoster virus: pathogenesis of human disease, the virus and viral replication, and the major viral glycoproteins. In: Hyman RW (ed) Natural History of Varicella Zoster Virus. Boca Raton: CRC Press, p. 1–65.Google Scholar
  23. Grose C, WE Friedrichs (1982) Immunoprecipitable polypeptides specified by varicella-zoster virus. Virology 118: 86–95.PubMedCrossRefGoogle Scholar
  24. Grose C, V Litwin (1988) Immunology of the varicella-zoster virus glycoproteins. J Infec Dis 157: 877–881.CrossRefGoogle Scholar
  25. Ho RJ, BT Rouse, L Huang (1986) Target sensitive immunoliposomes: preparation and sensitivation. Biochemistry 25: 5500–5506.PubMedCrossRefGoogle Scholar
  26. Hutto C, A Arvin, R Jacobs, R Steel, S Stagno, R Lyrene, L Willett, D Powell, R Andersen, J Werthammer, G Ratcliff, AJ Nahmias, C Christy, R Whitley (1987) Intrauterine herpes virus infections. J Pediatr 110: 97–101.PubMedCrossRefGoogle Scholar
  27. Ito M, T Ihara, C Grose, S Starr (1985) Human leukocytes kill varicella-zoster virus infected fibroblasts in the presence of murine monoclonal antibodies to virus specific glycoproteins. J Virol 54: 98.PubMedGoogle Scholar
  28. Keller PM, BJ Neff, RW Ellis (1986) Three major glycoprotein genes of varicella-zoster virus whose products have neutralization epitopes. J Virol 52: 293–297.Google Scholar
  29. Lee FK, RM Coleman, L Pereira, PD Bailey, M Tatsuno, AJ Nahmias (1985) Detection of herpes simplex virus type-2 specific antibody glycoprotein G. J Clin Microbiol 22: 641–644.PubMedGoogle Scholar
  30. Matsunaga Y, K Yamanishi, M Takahashi (1982) Experimental infection and immune response of guinea pigs with varicella-zoster virus. Infect Immun 37: 407–412.PubMedGoogle Scholar
  31. McGeoch DJ, HWM Moss, D McNab, MC Frame (1987) DNA sequence and genetic content of the HindIll 1 region in the short unique component of the herpes simplex virus type 2 genome: identification of the gene encoding glycoprotein G, and evolutionary comparisons. J Gen Virol 68: 19–38.Google Scholar
  32. Mertz GJ, RW Coombs, R Ashley, J Jourden, M Remington, C Winter, A Fahnlander, M Guinan, H Ducey, L Corey (1988) Transmission of genital herpes in couples with one symptomatic and one asymptomatic partner; a prospective study. J Infect Dis 157:: 1169–1177.Google Scholar
  33. Miller A. (1980) Selective decline in cellular immune response to varicella-zoster in the elderly. Neurology 30: 582–587.PubMedCrossRefGoogle Scholar
  34. Myers MG, LR Stanberry, BJ Edmond (1985) Varicella-zoster virus infection of strain 2 guinea pigs. J Infect Dis 151: 106–113.PubMedCrossRefGoogle Scholar
  35. Nahmias AJ, HH Keyserling, G Kerrick (1983) Herpes Simplex. In: Remington JS, JO Klein (eds) Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, WB Saunders, p. 156–190.Google Scholar
  36. Nahmias AJ, H Keyserling, R Bain (1985) Prevalence of herpes simplex virus type-specific antibodies in a USA prepaid medical practice population. Abstract, 6th International Society for STD Research.Google Scholar
  37. Pachl C, RL Burke, LL Stuve, L Sanchez-Pescador, G Van Nest, F Masiarz, D Dina (1987) Expression of cell-associated and secreted forms of herpes simplex virus type 1 glycoprotein gB in mammalian cells. J Virol 61: 315–325.PubMedGoogle Scholar
  38. Palumbo PE, AM Arvin, CM Koropchak, AE Wittek (1984) Investigation of varicella-zoster virus infected cell proteins that elicit antibody production during primary varicella using the immune transfer method. J Gen Virol 65: 2141.PubMedCrossRefGoogle Scholar
  39. Preblud SR. (1981) Age-specific risks of varicella complications. Pediatrics 68: 14–17.PubMedGoogle Scholar
  40. Prober CG, PA Hensleigh, FD Boucher, LL Yasukawa, DS Au, AM Arvin (1988) Identification of neonates exposed to herpes simplex virus: the value of routine viral cultures at delivery. N Engl J Med, in press.Google Scholar
  41. Rasmussen LR, J Mullenax, M Nelson, TC Merigan (1985) Human cytomegalovirus polypeptides stimulate neutralizing antibody in vivo Virology 145: 186–190.Google Scholar
  42. Roizman B, B Norrild, C Chan, L Pereira (1984) Identification and preliminary mapping with monoclonal antibodies of herpes simplex virus 2 glycoprotein lacking a known type 1 counterpart. Virology 133: 242–247PubMedCrossRefGoogle Scholar
  43. Shiraki K, RW Hyman (1987) The immediate early proteins of varicella zoster virus. Virology 156: 423–426.PubMedCrossRefGoogle Scholar
  44. Sullender WM, LL Yasukawa, M Schwartz, L Pereira, PA Hensleigh, CG Prober, AM Arvin (1988) type specific antibodies to herpes simplex virus-2 glycoprotein G in pregnant women, infants exposed to maternal HSV-2 infection at delivery and infants with neonatal herpes. J Infect Dis. 157: 164–171.Google Scholar
  45. Townsend AR, J Rothbard, FM Gotch, G Bahadur, D Wraith, AJ McMichael (1986(The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959–968.Google Scholar
  46. Weigle KA, C Grose (1984) Molecular dissection of the humoral immune response to individual varicella-zoster viral proteins during chickenpox, quiescence, reinfection, and reactivation. J Infect Dis 149: 741–749.PubMedCrossRefGoogle Scholar
  47. Whitley RJ, AJ Nahmias, AM Visintine, CL Fleming, CA Alford (1980) The natural history of herpes simplex virus infection of mother and newborn. Pediatrics 66: 796–800.Google Scholar
  48. Yeager AS, AM Arvin (1984) Reasons for absence of a history of recurrent genital infections in mothers of neonates infected with herpes simplex viruses. Pediatrics 73: 188–193.PubMedGoogle Scholar
  49. Yewdell JW, JR Bennick, M Mackett, L Lefrancois, DS Lyles, B Moss (1986) Recognition of cloned vesicular stomatitis virus internal and external gene products by cytotoxic T lymphocytes. J Exp Med 163: 1529 1534.Google Scholar
  50. Zarling JM, PA Moran, LA Lasky, B Moss (1986) Herpes simplex virus specific human T-cell clones recognize HSV glycoprotein D expressed by a recombinant vaccinia virus. J Virol 59: 506–509.PubMedGoogle Scholar
  51. Zweerink HJ, L Corey (1982) Virus specific antibodies in patients with genital herpes simplex virus infections. Infect Immun 37: 413–421.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Ann M. Arvin
    • 1
  • Wayne M. Sullender
    • 1
  • Francois Boucher
    • 1
  • Pamela S. Diaz
    • 1
  • Paul A. Hensleigh
    • 1
  • Charles G. Prober
    • 1
  1. 1.Infectious Disease Division, Department of Pediatrics and Department of Obstetrics and GynecologyStanford University School of MedicineStanfordUSA

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