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. 1997 May;71(5):3534–3544. doi: 10.1128/jvi.71.5.3534-3544.1997

Immunization with a replication-deficient mutant of herpes simplex virus type 1 (HSV-1) induces a CD8+ cytotoxic T-lymphocyte response and confers a level of protection comparable to that of wild-type HSV-1.

M A Brehm 1, R H Bonneau 1, D M Knipe 1, S S Tevethia 1
PMCID: PMC191500  PMID: 9094625

Abstract

Replication-deficient viruses provide an attractive alternative to conventional approaches used in the induction of antiviral immunity. We have quantitatively evaluated both the primary and memory cytotoxic T-lymphocyte (CTL) responses elicited by immunization with a replication-deficient mutant of herpes simplex virus type 1 (HSV-1). In addition, we have examined the potential role of these CTL in protection against HSV infection. Using bulk culture analysis and limiting-dilution analysis, we have shown that a replication-deficient virus, d301, generates a strong primary CTL response that is comparable to the response induced by the wild type-strain, KOS1.1. Furthermore, the CTL induced by d301 immunization recognized the immunodominant, H-2Kb-restricted, CTL recognition epitope gB498-505 to a level similar to that for CTL from KOS1.1-immunized mice. The memory CTL response evoked by d301 was strong and persistent, even though the frequencies of CTL were slightly lower than the frequencies of CTL induced by KOS1.1. Adoptive transfer studies indicated that both the CD8+ and the CD4+ T-cell responses generated by immunization with d301 and KOS1.1 were able to limit the extent of a cutaneous HSV infection to comparable levels. Overall, these results indicate that viral replication is not necessary to elicit a potent and durable HSV-specific immune response and suggest that replication-deficient viruses may be effective in eliciting protection against viral pathogens.

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Selected References

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

  1. Babu J. S., Thomas J., Kanangat S., Morrison L. A., Knipe D. M., Rouse B. T. Viral replication is required for induction of ocular immunopathology by herpes simplex virus. J Virol. 1996 Jan;70(1):101–107. doi: 10.1128/jvi.70.1.101-107.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Banks T. A., Nair S., Rouse B. T. Recognition by and in vitro induction of cytotoxic T lymphocytes against predicted epitopes of the immediate-early protein ICP27 of herpes simplex virus. J Virol. 1993 Jan;67(1):613–616. doi: 10.1128/jvi.67.1.613-616.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blacklaws B. A., Krishna S., Minson A. C., Nash A. A. Immunogenicity of herpes simplex virus type 1 glycoproteins expressed in vaccinia virus recombinants. Virology. 1990 Aug;177(2):727–736. doi: 10.1016/0042-6822(90)90539-4. [DOI] [PubMed] [Google Scholar]
  4. Blacklaws B. A., Nash A. A., Darby G. Specificity of the immune response of mice to herpes simplex virus glycoproteins B and D constitutively expressed on L cell lines. J Gen Virol. 1987 Apr;68(Pt 4):1103–1114. doi: 10.1099/0022-1317-68-4-1103. [DOI] [PubMed] [Google Scholar]
  5. Blacklaws B. A., Nash A. A. Immunological memory to herpes simplex virus type 1 glycoproteins B and D in mice. J Gen Virol. 1990 Apr;71(Pt 4):863–871. doi: 10.1099/0022-1317-71-4-863. [DOI] [PubMed] [Google Scholar]
  6. Bonneau R. H., Fu T. M., Tevethia S. S. In vivo priming and activation of memory cytotoxic T-lymphocytes (CTL) by a chimeric simian virus 40 T antigen expressing an eight amino acid residue herpes simplex virus gB CTL epitope. Virology. 1993 Dec;197(2):782–787. doi: 10.1006/viro.1993.1657. [DOI] [PubMed] [Google Scholar]
  7. Bonneau R. H., Jennings S. R. Herpes simplex virus-specific cytolytic T lymphocytes restricted to a normally low responder H-2 allele are protective in vivo. Virology. 1990 Feb;174(2):599–604. doi: 10.1016/0042-6822(90)90113-6. [DOI] [PubMed] [Google Scholar]
  8. Bonneau R. H., Jennings S. R. Modulation of acute and latent herpes simplex virus infection in C57BL/6 mice by adoptive transfer of immune lymphocytes with cytolytic activity. J Virol. 1989 Mar;63(3):1480–1484. doi: 10.1128/jvi.63.3.1480-1484.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bonneau R. H., Salvucci L. A., Johnson D. C., Tevethia S. S. Epitope specificity of H-2Kb-restricted, HSV-1-, and HSV-2-cross-reactive cytotoxic T lymphocyte clones. Virology. 1993 Jul;195(1):62–70. doi: 10.1006/viro.1993.1346. [DOI] [PubMed] [Google Scholar]
  10. Bonneau R. H., Sheridan J. F., Feng N. G., Glaser R. Stress-induced effects on cell-mediated innate and adaptive memory components of the murine immune response to herpes simplex virus infection. Brain Behav Immun. 1991 Sep;5(3):274–295. doi: 10.1016/0889-1591(91)90023-4. [DOI] [PubMed] [Google Scholar]
  11. Bouley D. M., Kanangat S., Wire W., Rouse B. T. Characterization of herpes simplex virus type-1 infection and herpetic stromal keratitis development in IFN-gamma knockout mice. J Immunol. 1995 Oct 15;155(8):3964–3971. [PubMed] [Google Scholar]
  12. Burke R. L., Goldbeck C., Ng P., Stanberry L., Ott G., Van Nest G. The influence of adjuvant on the therapeutic efficacy of a recombinant genital herpes vaccine. J Infect Dis. 1994 Nov;170(5):1110–1119. doi: 10.1093/infdis/170.5.1110. [DOI] [PubMed] [Google Scholar]
  13. Cantin E. M., Eberle R., Baldick J. L., Moss B., Willey D. E., Notkins A. L., Openshaw H. Expression of herpes simplex virus 1 glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal herpes simplex virus 1 infection. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5908–5912. doi: 10.1073/pnas.84.16.5908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Carter V. C., Schaffer P. A., Tevethia S. S. The involvement of herpes simplex virus type 1 glycoproteins in cell-mediated immunity. J Immunol. 1981 May;126(5):1655–1660. [PubMed] [Google Scholar]
  15. Dix R. D., Pereira L., Baringer J. R. Use of monoclonal antibody directed against herpes simplex virus glycoproteins to protect mice against acute virus-induced neurological disease. Infect Immun. 1981 Oct;34(1):192–199. doi: 10.1128/iai.34.1.192-199.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Farrell H. E., McLean C. S., Harley C., Efstathiou S., Inglis S., Minson A. C. Vaccine potential of a herpes simplex virus type 1 mutant with an essential glycoprotein deleted. J Virol. 1994 Feb;68(2):927–932. doi: 10.1128/jvi.68.2.927-932.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Fu T. M., Bonneau R. H., Epler M., Tevethia M. J., Alam S., Verner K., Tevethia S. S. Induction and persistence of a cytotoxic T lymphocyte (CTL) response against a herpes simplex virus-specific CTL epitope expressed in a cellular protein. Virology. 1996 Aug 1;222(1):269–274. doi: 10.1006/viro.1996.0419. [DOI] [PubMed] [Google Scholar]
  19. Gallichan W. S., Johnson D. C., Graham F. L., Rosenthal K. L. Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B. J Infect Dis. 1993 Sep;168(3):622–629. doi: 10.1093/infdis/168.3.622. [DOI] [PubMed] [Google Scholar]
  20. Gao M., Knipe D. M. Genetic evidence for multiple nuclear functions of the herpes simplex virus ICP8 DNA-binding protein. J Virol. 1989 Dec;63(12):5258–5267. doi: 10.1128/jvi.63.12.5258-5267.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ghiasi H., Cai S., Slanina S., Nesburn A. B., Wechsler S. L. Vaccination of mice with herpes simplex virus type 1 glycoprotein D DNA produces low levels of protection against lethal HSV-1 challenge. Antiviral Res. 1995 Oct;28(2):147–157. doi: 10.1016/0166-3542(95)00045-n. [DOI] [PubMed] [Google Scholar]
  22. Ghiasi H., Kaiwar R., Nesburn A. B., Slanina S., Wechsler S. L. Baculovirus-expressed glycoprotein E (gE) of herpes simplex virus type-1 (HSV-1) protects mice against lethal intraperitoneal and lethal ocular HSV-1 challenge. Virology. 1992 Jun;188(2):469–476. doi: 10.1016/0042-6822(92)90500-o. [DOI] [PubMed] [Google Scholar]
  23. Ghiasi H., Kaiwar R., Nesburn A. B., Slanina S., Wechsler S. L. Expression of seven herpes simplex virus type 1 glycoproteins (gB, gC, gD, gE, gG, gH, and gI): comparative protection against lethal challenge in mice. J Virol. 1994 Apr;68(4):2118–2126. doi: 10.1128/jvi.68.4.2118-2126.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ghiasi H., Kaiwar R., Nesburn A. B., Wechsler S. L. Baculovirus-expressed glycoprotein G of herpes simplex virus type 1 partially protects vaccinated mice against lethal HSV-1 challenge. Virology. 1992 Sep;190(1):233–239. doi: 10.1016/0042-6822(92)91209-d. [DOI] [PubMed] [Google Scholar]
  25. Glorioso J., Kees U., Kümel G., Kirchner H., Krammer P. H. Identification of herpes simplex virus type 1 (HSV-1) glycoprotein gC as the immunodominant antigen for HSV-1-specific memory cytotoxic T lymphocytes. J Immunol. 1985 Jul;135(1):575–582. [PubMed] [Google Scholar]
  26. Hanke T., Graham F. L., Rosenthal K. L., Johnson D. C. Identification of an immunodominant cytotoxic T-lymphocyte recognition site in glycoprotein B of herpes simplex virus by using recombinant adenovirus vectors and synthetic peptides. J Virol. 1991 Mar;65(3):1177–1186. doi: 10.1128/jvi.65.3.1177-1186.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hengel H., Lindner M., Wagner H., Heeg K. Frequency of herpes simplex virus-specific murine cytotoxic T lymphocyte precursors in mitogen- and antigen-driven primary in vitro T cell responses. J Immunol. 1987 Dec 15;139(12):4196–4202. [PubMed] [Google Scholar]
  28. Hou S., Hyland L., Ryan K. W., Portner A., Doherty P. C. Virus-specific CD8+ T-cell memory determined by clonal burst size. Nature. 1994 Jun 23;369(6482):652–654. doi: 10.1038/369652a0. [DOI] [PubMed] [Google Scholar]
  29. Igietseme J. U., Calzada P. J., Gonzalez A. R., Streilein J. W., Atherton S. S. Protection of mice from herpes simplex virus-induced retinitis by in vitro-activated immune cells. J Virol. 1989 Nov;63(11):4808–4813. doi: 10.1128/jvi.63.11.4808-4813.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jennings S. R., Bonneau R. H., Smith P. M., Wolcott R. M., Chervenak R. CD4-positive T lymphocytes are required for the generation of the primary but not the secondary CD8-positive cytolytic T lymphocyte response to herpes simplex virus in C57BL/6 mice. Cell Immunol. 1991 Mar;133(1):234–252. doi: 10.1016/0008-8749(91)90194-g. [DOI] [PubMed] [Google Scholar]
  31. Jennings S. R., Fresa K. L., Lippe P. A., Milici J. E., Tevethia S. S. Frequency analysis of simian virus 40-specific cytotoxic T lymphocyte precursors in the high responder C57BL/6 mouse strain. J Gen Virol. 1988 Oct;69(Pt 10):2493–2503. doi: 10.1099/0022-1317-69-10-2493. [DOI] [PubMed] [Google Scholar]
  32. Jennings S. R., Rice P. L., Kloszewski E. D., Anderson R. W., Thompson D. L., Tevethia S. S. Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells. J Virol. 1985 Dec;56(3):757–766. doi: 10.1128/jvi.56.3.757-766.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jennings S. R., Rice P. L., Pan S., Knowles B. B., Tevethia S. S. Recognition of herpes simplex virus antigens on the surface of mouse cells of the H-2b haplotype by virus-specific cytotoxic T lymphocytes. J Immunol. 1984 Jan;132(1):475–481. [PubMed] [Google Scholar]
  34. 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]
  35. Kapoor A. K., Nash A. A., Wildy P., Phelan J., McLean C. S., Field H. J. Pathogenesis of herpes simplex virus in congenitally athymic mice: the relative roles of cell-mediated and humoral immunity. J Gen Virol. 1982 Jun;60(Pt 2):225–233. doi: 10.1099/0022-1317-60-2-225. [DOI] [PubMed] [Google Scholar]
  36. Kierstead T. D., Tevethia M. J. Association of p53 binding and immortalization of primary C57BL/6 mouse embryo fibroblasts by using simian virus 40 T-antigen mutants bearing internal overlapping deletion mutations. J Virol. 1993 Apr;67(4):1817–1829. doi: 10.1128/jvi.67.4.1817-1829.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Krishna S., Blacklaws B. A., Overton H. A., Bishop D. H., Nash A. A. Expression of glycoprotein D of herpes simplex virus type 1 in a recombinant baculovirus: protective responses and T cell recognition of the recombinant-infected cell extracts. J Gen Virol. 1989 Jul;70(Pt 7):1805–1814. doi: 10.1099/0022-1317-70-7-1805. [DOI] [PubMed] [Google Scholar]
  38. Langenberg A. G., Burke R. L., Adair S. F., Sekulovich R., Tigges M., Dekker C. L., Corey L. A recombinant glycoprotein vaccine for herpes simplex virus type 2: safety and immunogenicity [corrected]. Ann Intern Med. 1995 Jun 15;122(12):889–898. doi: 10.7326/0003-4819-122-12-199506150-00001. [DOI] [PubMed] [Google Scholar]
  39. Larsen H. S., Feng M. F., Horohov D. W., Moore R. N., Rouse B. T. Role of T-lymphocyte subsets in recovery from herpes simplex virus infection. J Virol. 1984 Apr;50(1):56–59. doi: 10.1128/jvi.50.1.56-59.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Larsen H. S., Russell R. G., Rouse B. T. Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic T lymphocytes. Infect Immun. 1983 Jul;41(1):197–204. doi: 10.1128/iai.41.1.197-204.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lawman M. J., Rouse B. T., Courtney R. J., Walker R. D. Cell-mediated immunity against herpes simplex induction of cytotoxic T lymphocytes. Infect Immun. 1980 Jan;27(1):133–139. doi: 10.1128/iai.27.1.133-139.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Manickan E., Francotte M., Kuklin N., Dewerchin M., Molitor C., Gheysen D., Slaoui M., Rouse B. T. Vaccination with recombinant vaccinia viruses expressing ICP27 induces protective immunity against herpes simplex virus through CD4+ Th1+ T cells. J Virol. 1995 Aug;69(8):4711–4716. doi: 10.1128/jvi.69.8.4711-4716.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Manickan E., Rouse B. T. Roles of different T-cell subsets in control of herpes simplex virus infection determined by using T-cell-deficient mouse-models. J Virol. 1995 Dec;69(12):8178–8179. doi: 10.1128/jvi.69.12.8178-8179.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Manickan E., Rouse R. J., Yu Z., Wire W. S., Rouse B. T. Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes. J Immunol. 1995 Jul 1;155(1):259–265. [PubMed] [Google Scholar]
  45. Martin S., Moss B., Berman P. W., Laskey L. A., Rouse B. T. Mechanisms of antiviral immunity induced by a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: cytotoxic T cells. J Virol. 1987 Mar;61(3):726–734. doi: 10.1128/jvi.61.3.726-734.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Martin S., Rouse B. T. The mechanisms of antiviral immunity induced by a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: clearance of local infection. J Immunol. 1987 May 15;138(10):3431–3437. [PubMed] [Google Scholar]
  47. McDermott M. R., Graham F. L., Hanke T., Johnson D. C. Protection of mice against lethal challenge with herpes simplex virus by vaccination with an adenovirus vector expressing HSV glycoprotein B. Virology. 1989 Mar;169(1):244–247. doi: 10.1016/0042-6822(89)90064-0. [DOI] [PubMed] [Google Scholar]
  48. McLaughlin-Taylor E., Willey D. E., Cantin E. M., Eberle R., Moss B., Openshaw H. A recombinant vaccinia virus expressing herpes simplex virus type 1 glycoprotein B induces cytotoxic T lymphocytes in mice. J Gen Virol. 1988 Jul;69(Pt 7):1731–1734. doi: 10.1099/0022-1317-69-7-1731. [DOI] [PubMed] [Google Scholar]
  49. McLean C. S., Erturk M., Jennings R., Challanain D. N., Minson A. C., Duncan I., Boursnell M. E., Inglis S. C. Protective vaccination against primary and recurrent disease caused by herpes simplex virus (HSV) type 2 using a genetically disabled HSV-1. J Infect Dis. 1994 Nov;170(5):1100–1109. doi: 10.1093/infdis/170.5.1100. [DOI] [PubMed] [Google Scholar]
  50. Meignier B. Genetically engineered attenuated herpes simplex viruses. Rev Infect Dis. 1991 Nov-Dec;13 (Suppl 11):S895–S897. doi: 10.1093/clind/13.supplement_11.s895. [DOI] [PubMed] [Google Scholar]
  51. Mitchell B. M., Stevens J. G. Neuroinvasive properties of herpes simplex virus type 1 glycoprotein variants are controlled by the immune response. J Immunol. 1996 Jan 1;156(1):246–255. [PubMed] [Google Scholar]
  52. Morrison L. A., Knipe D. M. Immunization with replication-defective mutants of herpes simplex virus type 1: sites of immune intervention in pathogenesis of challenge virus infection. J Virol. 1994 Feb;68(2):689–696. doi: 10.1128/jvi.68.2.689-696.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Morrison L. A., Knipe D. M. Mechanisms of immunization with a replication-defective mutant of herpes simplex virus 1. Virology. 1996 Jun 15;220(2):402–413. doi: 10.1006/viro.1996.0328. [DOI] [PubMed] [Google Scholar]
  54. Nash A. A., Field H. J., Quartey-Papafio R. Cell-mediated immunity in herpes simplex virus-infected mice: induction, characterization and antiviral effects of delayed type hypersensitivity. J Gen Virol. 1980 Jun;48(Pt 2):351–357. doi: 10.1099/0022-1317-48-2-351. [DOI] [PubMed] [Google Scholar]
  55. Nash A. A., Phelan J., Wildy P. Cell-mediated immunity in herpes simplex virus-infected mice: H-2 mapping of the delayed-type hypersensitivity response and the antiviral T cell response. J Immunol. 1981 Apr;126(4):1260–1262. [PubMed] [Google Scholar]
  56. Nash A. A., Quartey-Papafio R., Wildy P. Cell-mediated immunity in herpes simplex virus-infected mice: functional analysis of lymph node cells during periods of acute and latent infection, with reference to cytotoxic and memory cells. J Gen Virol. 1980 Aug;49(2):309–317. doi: 10.1099/0022-1317-49-2-309. [DOI] [PubMed] [Google Scholar]
  57. Nguyen L. H., Knipe D. M., Finberg R. W. Replication-defective mutants of herpes simplex virus (HSV) induce cellular immunity and protect against lethal HSV infection. J Virol. 1992 Dec;66(12):7067–7072. doi: 10.1128/jvi.66.12.7067-7072.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Nugent C. T., Wolcott R. M., Chervenak R., Jennings S. R. Analysis of the cytolytic T-lymphocyte response to herpes simplex virus type 1 glycoprotein B during primary and secondary infection. J Virol. 1994 Nov;68(11):7644–7648. doi: 10.1128/jvi.68.11.7644-7648.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Pfizenmaier K., Jung H., Starzinski-Powitz A., Röllinghoff M., Wagner H. The role of T cells in anti-herpes simplex virus immunity. I. Induction of antigen-specific cytotoxic T lymphocytes. J Immunol. 1977 Sep;119(3):939–944. [PubMed] [Google Scholar]
  60. Pfizenmaier K., Starzinski-Powitz A., Röllinghoff M., Falks D., Wagner H. T-cell-mediated cytotoxicity against herpes simplex virus-infected target cells. Nature. 1977 Feb 17;265(5595):630–632. doi: 10.1038/265630a0. [DOI] [PubMed] [Google Scholar]
  61. Posavad C. M., Koelle D. M., Corey L. High frequency of CD8+ cytotoxic T-lymphocyte precursors specific for herpes simplex viruses in persons with genital herpes. J Virol. 1996 Nov;70(11):8165–8168. doi: 10.1128/jvi.70.11.8165-8168.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Pretell J., Greenfield R. S., Tevethia S. S. Biology of simian virus 40 (SV40) transplantation antigen (TrAg). V In vitro demonstration of SV40 TrAg in SV40 infected nonpermissive mouse cells by the lymphocyte mediated cytotoxicity assay. Virology. 1979 Aug;97(1):32–41. doi: 10.1016/0042-6822(79)90370-2. [DOI] [PubMed] [Google Scholar]
  63. Rinaldo C. R., Jr, Torpey D. J., 3rd Cell-mediated immunity and immunosuppression in herpes simplex virus infection. Immunodeficiency. 1993;5(1):33–90. [PubMed] [Google Scholar]
  64. Rosenthal K. L., Smiley J. R., South S., Johnson D. C. Cells expressing herpes simplex virus glycoprotein gC but not gB, gD, or gE are recognized by murine virus-specific cytotoxic T lymphocytes. J Virol. 1987 Aug;61(8):2438–2447. doi: 10.1128/jvi.61.8.2438-2447.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Rouse B. T., Larsen H. S., Wagner H. Frequency of cytotoxic T lymphocyte precursors to herpes simplex virus type 1 as determined by limiting dilution analysis. Infect Immun. 1983 Feb;39(2):785–792. doi: 10.1128/iai.39.2.785-792.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Schmid D. S., Rouse B. T. The role of T cell immunity in control of herpes simplex virus. Curr Top Microbiol Immunol. 1992;179:57–74. doi: 10.1007/978-3-642-77247-4_4. [DOI] [PubMed] [Google Scholar]
  67. Sethi K. K., Omata Y., Schneweis K. E. Protection of mice from fatal herpes simplex virus type 1 infection by adoptive transfer of cloned virus-specific and H-2-restricted cytotoxic T lymphocytes. J Gen Virol. 1983 Feb;64(Pt 2):443–447. doi: 10.1099/0022-1317-64-2-443. [DOI] [PubMed] [Google Scholar]
  68. Simmons A., Nash A. A. Role of antibody in primary and recurrent herpes simplex virus infection. J Virol. 1985 Mar;53(3):944–948. doi: 10.1128/jvi.53.3.944-948.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Simmons A., Tscharke D. C. Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. J Exp Med. 1992 May 1;175(5):1337–1344. doi: 10.1084/jem.175.5.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Smith P. M., Wolcott R. M., Chervenak R., Jennings S. R. Control of acute cutaneous herpes simplex virus infection: T cell-mediated viral clearance is dependent upon interferon-gamma (IFN-gamma). Virology. 1994 Jul;202(1):76–88. doi: 10.1006/viro.1994.1324. [DOI] [PubMed] [Google Scholar]
  71. Straus S. E., Corey L., Burke R. L., Savarese B., Barnum G., Krause P. R., Kost R. G., Meier J. L., Sekulovich R., Adair S. F. Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet. 1994 Jun 11;343(8911):1460–1463. doi: 10.1016/s0140-6736(94)92581-x. [DOI] [PubMed] [Google Scholar]
  72. Tanaka Y., Tevethia S. S. In vitro selection of SV40 T antigen epitope loss variants by site-specific cytotoxic T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4348–4354. [PubMed] [Google Scholar]
  73. Tanaka Y., Tevethia S. S. Loss of immunorecessive cytotoxic T lymphocyte determinant V on SV40 T antigen following cocultivation with site-specific cytotoxic T lymphocyte clone Y-5. Intervirology. 1990;31(2-4):197–202. doi: 10.1159/000150154. [DOI] [PubMed] [Google Scholar]
  74. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol. 1981 Apr;126(4):1614–1619. [PubMed] [Google Scholar]
  75. Walker C., Selby M., Erickson A., Cataldo D., Valensi J. P., Van Nest G. V. Cationic lipids direct a viral glycoprotein into the class I major histocompatibility complex antigen-presentation pathway. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7915–7918. doi: 10.1073/pnas.89.17.7915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Ward P. L., Roizman B. Herpes simplex genes: the blueprint of a successful human pathogen. Trends Genet. 1994 Aug;10(8):267–274. doi: 10.1016/0168-9525(90)90009-u. [DOI] [PubMed] [Google Scholar]
  77. Wu L., Morahan P. S. Macrophages and other nonspecific defenses: role in modulating resistance against herpes simplex virus. Curr Top Microbiol Immunol. 1992;179:89–110. doi: 10.1007/978-3-642-77247-4_6. [DOI] [PubMed] [Google Scholar]

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