Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons (original) (raw)

Abstract

The role of CD8+ T cells in resistance to herpes simplex virus (HSV) was examined. After cutaneous inoculation, HSV spreads to the peripheral nervous system (PNS) where it replicates in ganglionic neurons. In normal mice, replication of virus in the PNS was rapidly terminated and evidence of neuronal destruction, assessed by a quantitative histological assay, was sparse. Clearance of infectious virus was impaired, and a strikingly high proportion of ganglionic neurons was killed, in mice treated with an antibody that depleted them of CD8+ T cells. These results suggest that CD8+ T cells play an important role in maintaining the integrity of the sensory nervous system during primary infection with HSV. Therefore, viral epitopes recognized by CD8+ T cells and restricting class I major histocompatibility complex genes are, in principle, implicated as interacting genetic determinants of neurovirulence.

Full Text

The Full Text of this article is available as a PDF (2.1 MB).

Selected References

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

  1. Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. doi: 10.1038/312548a0. [DOI] [PubMed] [Google Scholar]
  2. Cook M. L., Bastone V. B., Stevens J. G. Evidence that neurons harbor latent herpes simplex virus. Infect Immun. 1974 May;9(5):946–951. doi: 10.1128/iai.9.5.946-951.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cook M. L., Stevens J. G. Pathogenesis of herpetic neuritis and ganglionitis in mice: evidence for intra-axonal transport of infection. Infect Immun. 1973 Feb;7(2):272–288. doi: 10.1128/iai.7.2.272-288.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dillard S. H., Cheatham W. J., Moses H. L. Electron microscopy of zosteriform herpes simplex infection in the mouse. Lab Invest. 1972 Apr;26(4):391–402. [PubMed] [Google Scholar]
  5. Efstathiou S., Minson A. C., Field H. J., Anderson J. R., Wildy P. Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans. J Virol. 1986 Feb;57(2):446–455. doi: 10.1128/jvi.57.2.446-455.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. HOPE-SIMPSON R. E. THE NATURE OF HERPES ZOSTER: A LONG-TERM STUDY AND A NEW HYPOTHESIS. Proc R Soc Med. 1965 Jan;58:9–20. [PMC free article] [PubMed] [Google Scholar]
  7. Hill T. J., Field H. J., Blyth W. A. Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. J Gen Virol. 1975 Sep;28(3):341–353. doi: 10.1099/0022-1317-28-3-341. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Joly E., Mucke L., Oldstone M. B. Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science. 1991 Sep 13;253(5025):1283–1285. doi: 10.1126/science.1891717. [DOI] [PubMed] [Google Scholar]
  10. Leib D. A., Coen D. M., Bogard C. L., Hicks K. A., Yager D. R., Knipe D. M., Tyler K. L., Schaffer P. A. Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. J Virol. 1989 Feb;63(2):759–768. doi: 10.1128/jvi.63.2.759-768.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lengyel P. Biochemistry of interferons and their actions. Annu Rev Biochem. 1982;51:251–282. doi: 10.1146/annurev.bi.51.070182.001343. [DOI] [PubMed] [Google Scholar]
  12. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. Antibody-mediated clearance of alphavirus infection from neurons. Science. 1991 Nov 8;254(5033):856–860. doi: 10.1126/science.1658936. [DOI] [PubMed] [Google Scholar]
  13. Maheshwari R. K., Friedman R. M. Assay of effect of interferon on viruses that bud from plasma membrane. Methods Enzymol. 1981;79(Pt B):451–458. doi: 10.1016/s0076-6879(81)79058-x. [DOI] [PubMed] [Google Scholar]
  14. Marrack P., Kappler J. The T cell receptor. Science. 1987 Nov 20;238(4830):1073–1079. doi: 10.1126/science.3317824. [DOI] [PubMed] [Google Scholar]
  15. McLean C., Buckmaster A., Hancock D., Buchan A., Fuller A., Minson A. Monoclonal antibodies to three non-glycosylated antigens of herpes simplex virus type 2. J Gen Virol. 1982 Dec;63(2):297–305. doi: 10.1099/0022-1317-63-2-297. [DOI] [PubMed] [Google Scholar]
  16. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  17. Nash A. A., Jayasuriya A., Phelan J., Cobbold S. P., Waldmann H., Prospero T. Different roles for L3T4+ and Lyt 2+ T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system. J Gen Virol. 1987 Mar;68(Pt 3):825–833. doi: 10.1099/0022-1317-68-3-825. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Pircher H., Moskophidis D., Rohrer U., Bürki K., Hengartner H., Zinkernagel R. M. Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature. 1990 Aug 16;346(6285):629–633. doi: 10.1038/346629a0. [DOI] [PubMed] [Google Scholar]
  21. RUSSELL W. C. A sensitive and precise plaque assay for herpes virus. Nature. 1962 Sep 8;195:1028–1029. doi: 10.1038/1951028a0. [DOI] [PubMed] [Google Scholar]
  22. Simmons A. H-2-linked genes influence the severity of herpes simplex virus infection of the peripheral nervous system. J Exp Med. 1989 Apr 1;169(4):1503–1507. doi: 10.1084/jem.169.4.1503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Simmons A., La Vista A. B. Neural infection in mice after cutaneous inoculation with HSV-1 is under complex host genetic control. Virus Res. 1989 Jul;13(3):263–270. doi: 10.1016/0168-1702(89)90020-8. [DOI] [PubMed] [Google Scholar]
  24. Simmons A., Nash A. A. Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease. J Virol. 1984 Dec;52(3):816–821. doi: 10.1128/jvi.52.3.816-821.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smolen A. J., Wright L. L., Cunningham T. J. Neuron numbers in the superior cervical sympathetic ganglion of the rat: a critical comparison of methods for cell counting. J Neurocytol. 1983 Oct;12(5):739–750. doi: 10.1007/BF01258148. [DOI] [PubMed] [Google Scholar]
  26. Speck P. G., Simmons A. Divergent molecular pathways of productive and latent infection with a virulent strain of herpes simplex virus type 1. J Virol. 1991 Aug;65(8):4001–4005. doi: 10.1128/jvi.65.8.4001-4005.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steiner I., Kennedy P. G. Herpes simplex virus latency in the nervous system--a new model. Neuropathol Appl Neurobiol. 1991 Dec;17(6):433–440. doi: 10.1111/j.1365-2990.1991.tb00747.x. [DOI] [PubMed] [Google Scholar]
  28. Weinstein D. L., Walker D. G., Akiyama H., McGeer P. L. Herpes simplex virus type I infection of the CNS induces major histocompatibility complex antigen expression on rat microglia. J Neurosci Res. 1990 May;26(1):55–65. doi: 10.1002/jnr.490260107. [DOI] [PubMed] [Google Scholar]
  29. Wong G. H., Bartlett P. F., Clark-Lewis I., Battye F., Schrader J. W. Inducible expression of H-2 and Ia antigens on brain cells. Nature. 1984 Aug 23;310(5979):688–691. doi: 10.1038/310688a0. [DOI] [PubMed] [Google Scholar]