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. 1995 Dec;69(12):8127–8131. doi: 10.1128/jvi.69.12.8127-8131.1995

CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity.

R F Castro 1, S Perlman 1
PMCID: PMC189767  PMID: 7494335

Abstract

CD8+ T cells with cytotoxic activity against the surface glycoprotein (S) of mouse hepatitis virus, strain JHM, have been identified in the central nervous system (CNS) of both acutely and chronically infected C57BL/6 mice. In this report, two specific epitopes recognized by these CNS-derived cells were identified, using a panel of peptides chosen because they conformed to the allele-specific binding motif for MHC class I H-2Kb and H-2Db. The active peptides encompassed residues 510 to 518 (CSLWNGPHL, H-2Db) and 598 to 605 (RCQIFANI, H-2Kb). Both epitopes are located within the region of the S protein previously shown to be prone to deletion after passage in animals. These deleted strains are generally less neurovirulent than the wild-type virus but still are able to cause demyelination. Since C57BL/6 mice become persistently infected more commonly than many other strains of mice, these data are consistent with a role for CD8+ T-cell escape mutants in the pathogenesis of the demyelinating disease. This is the first report of CD8+ T-cell epitope localization within the S protein, the protein most strongly implicated thus far in pathogenesis in the host.

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Selected References

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  1. Bertoletti A., Sette A., Chisari F. V., Penna A., Levrero M., De Carli M., Fiaccadori F., Ferrari C. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature. 1994 Jun 2;369(6479):407–410. doi: 10.1038/369407a0. [DOI] [PubMed] [Google Scholar]
  2. Buchmeier M. J., Lewicki H. A., Talbot P. J., Knobler R. L. Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology. 1984 Jan 30;132(2):261–270. doi: 10.1016/0042-6822(84)90033-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Castro R. F., Evans G. D., Jaszewski A., Perlman S. Coronavirus-induced demyelination occurs in the presence of virus-specific cytotoxic T cells. Virology. 1994 May 1;200(2):733–743. doi: 10.1006/viro.1994.1237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Couillin I., Culmann-Penciolelli B., Gomard E., Choppin J., Levy J. P., Guillet J. G., Saragosti S. Impaired cytotoxic T lymphocyte recognition due to genetic variations in the main immunogenic region of the human immunodeficiency virus 1 NEF protein. J Exp Med. 1994 Sep 1;180(3):1129–1134. doi: 10.1084/jem.180.3.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dalziel R. G., Lampert P. W., Talbot P. J., Buchmeier M. J. Site-specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence. J Virol. 1986 Aug;59(2):463–471. doi: 10.1128/jvi.59.2.463-471.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Elliott T., Smith M., Driscoll P., McMichael A. Peptide selection by class I molecules of the major histocompatibility complex. Curr Biol. 1993 Dec 1;3(12):854–866. doi: 10.1016/0960-9822(93)90219-e. [DOI] [PubMed] [Google Scholar]
  7. Falk K., Rötzschke O. Consensus motifs and peptide ligands of MHC class I molecules. Semin Immunol. 1993 Apr;5(2):81–94. doi: 10.1006/smim.1993.1012. [DOI] [PubMed] [Google Scholar]
  8. Fleming J. O., Shubin R. A., Sussman M. A., Casteel N., Stohlman S. A. Monoclonal antibodies to the matrix (E1) glycoprotein of mouse hepatitis virus protect mice from encephalitis. Virology. 1989 Jan;168(1):162–167. doi: 10.1016/0042-6822(89)90415-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fleming J. O., Trousdale M. D., Bradbury J., Stohlman S. A., Weiner L. P. Experimental demyelination induced by coronavirus JHM (MHV-4): molecular identification of a viral determinant of paralytic disease. Microb Pathog. 1987 Jul;3(1):9–20. doi: 10.1016/0882-4010(87)90033-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haspel M. V., Lampert P. W., Oldstone M. B. Temperature-sensitive mutants of mouse hepatitis virus produce a high incidence of demyelination. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4033–4036. doi: 10.1073/pnas.75.8.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Klavinskis L. S., Whitton J. L., Joly E., Oldstone M. B. Vaccination and protection from a lethal viral infection: identification, incorporation, and use of a cytotoxic T lymphocyte glycoprotein epitope. Virology. 1990 Oct;178(2):393–400. doi: 10.1016/0042-6822(90)90336-p. [DOI] [PubMed] [Google Scholar]
  13. Klenerman P., Rowland-Jones S., McAdam S., Edwards J., Daenke S., Lalloo D., Köppe B., Rosenberg W., Boyd D., Edwards A. Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants. Nature. 1994 Jun 2;369(6479):403–407. doi: 10.1038/369403a0. [DOI] [PubMed] [Google Scholar]
  14. Kulkarni A. B., Collins P. L., Bacik I., Yewdell J. W., Bennink J. R., Crowe J. E., Jr, Murphy B. R. Cytotoxic T cells specific for a single peptide on the M2 protein of respiratory syncytial virus are the sole mediators of resistance induced by immunization with M2 encoded by a recombinant vaccinia virus. J Virol. 1995 Feb;69(2):1261–1264. doi: 10.1128/jvi.69.2.1261-1264.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Körner H., Schliephake A., Winter J., Zimprich F., Lassmann H., Sedgwick J., Siddell S., Wege H. Nucleocapsid or spike protein-specific CD4+ T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+ T cells. J Immunol. 1991 Oct 1;147(7):2317–2323. [PubMed] [Google Scholar]
  16. La Monica N., Banner L. R., Morris V. L., Lai M. M. Localization of extensive deletions in the structural genes of two neurotropic variants of murine coronavirus JHM. Virology. 1991 Jun;182(2):883–888. doi: 10.1016/0042-6822(91)90635-O. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lai M. M. Coronavirus: organization, replication and expression of genome. Annu Rev Microbiol. 1990;44:303–333. doi: 10.1146/annurev.mi.44.100190.001511. [DOI] [PubMed] [Google Scholar]
  18. Lampert P. W., Sims J. K., Kniazeff A. J. Mechanism of demyelination in JHM virus encephalomyelitis. Electron microscopic studies. Acta Neuropathol. 1973 Mar 30;24(1):76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lecomte J., Cainelli-Gebara V., Mercier G., Mansour S., Talbot P. J., Lussier G., Oth D. Protection from mouse hepatitis virus type 3-induced acute disease by an anti-nucleoprotein monoclonal antibody. Brief report. Arch Virol. 1987;97(1-2):123–130. doi: 10.1007/BF01310740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mobley J., Evans G., Dailey M. O., Perlman S. Immune response to a murine coronavirus: identification of a homing receptor-negative CD4+ T cell subset that responds to viral glycoproteins. Virology. 1992 Apr;187(2):443–452. doi: 10.1016/0042-6822(92)90446-V. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moskophidis D., Zinkernagel R. M. Immunobiology of cytotoxic T-cell escape mutants of lymphocytic choriomeningitis virus. J Virol. 1995 Apr;69(4):2187–2193. doi: 10.1128/jvi.69.4.2187-2193.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nagashima K., Wege H., Meyermann R., ter Meulen V. Corona virus induced subacute demyelinating encephalomyelitis in rats: a morphological analysis. Acta Neuropathol. 1978 Oct 13;44(1):63–70. doi: 10.1007/BF00691641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nakanaga K., Yamanouchi K., Fujiwara K. Protective effect of monoclonal antibodies on lethal mouse hepatitis virus infection in mice. J Virol. 1986 Jul;59(1):168–171. doi: 10.1128/jvi.59.1.168-171.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nowak M. A., May R. M., Phillips R. E., Rowland-Jones S., Lalloo D. G., McAdam S., Klenerman P., Köppe B., Sigmund K., Bangham C. R. Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature. 1995 Jun 15;375(6532):606–611. doi: 10.1038/375606a0. [DOI] [PubMed] [Google Scholar]
  25. Parker S. E., Gallagher T. M., Buchmeier M. J. Sequence analysis reveals extensive polymorphism and evidence of deletions within the E2 glycoprotein gene of several strains of murine hepatitis virus. Virology. 1989 Dec;173(2):664–673. doi: 10.1016/0042-6822(89)90579-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Perlman S., Schelper R., Bolger E., Ries D. Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody. Microb Pathog. 1987 Mar;2(3):185–194. doi: 10.1016/0882-4010(87)90020-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Phillips R. E., Rowland-Jones S., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991 Dec 12;354(6353):453–459. doi: 10.1038/354453a0. [DOI] [PubMed] [Google Scholar]
  28. Schmidt I., Skinner M., Siddell S. Nucleotide sequence of the gene encoding the surface projection glycoprotein of coronavirus MHV-JHM. J Gen Virol. 1987 Jan;68(Pt 1):47–56. doi: 10.1099/0022-1317-68-1-47. [DOI] [PubMed] [Google Scholar]
  29. Sorensen O., Perry D., Dales S. In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. Arch Neurol. 1980 Aug;37(8):478–484. doi: 10.1001/archneur.1980.00500570026003. [DOI] [PubMed] [Google Scholar]
  30. Stohlman S. A., Bergmann C. C., van der Veen R. C., Hinton D. R. Mouse hepatitis virus-specific cytotoxic T lymphocytes protect from lethal infection without eliminating virus from the central nervous system. J Virol. 1995 Feb;69(2):684–694. doi: 10.1128/jvi.69.2.684-694.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stohlman S. A., Kyuwa S., Polo J. M., Brady D., Lai M. M., Bergmann C. C. Characterization of mouse hepatitis virus-specific cytotoxic T cells derived from the central nervous system of mice infected with the JHM strain. J Virol. 1993 Dec;67(12):7050–7059. doi: 10.1128/jvi.67.12.7050-7059.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stohlman S. A., Matsushima G. K., Casteel N., Weiner L. P. In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection but do not inhibit virus replication. J Immunol. 1986 Apr 15;136(8):3052–3056. [PubMed] [Google Scholar]
  33. Taguchi F., Kubo H., Takahashi H., Suzuki H. Localization of neurovirulence determinant for rats on the S1 subunit of murine coronavirus JHMV. Virology. 1995 Apr 1;208(1):67–74. doi: 10.1006/viro.1995.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wang F. I., Fleming J. O., Lai M. M. Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity. Virology. 1992 Feb;186(2):742–749. doi: 10.1016/0042-6822(92)90041-M. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weiner L. P. Pathogenesis of demyelination induced by a mouse hepatitis. Arch Neurol. 1973 May;28(5):298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]
  36. Whitton J. L., Sheng N., Oldstone M. B., McKee T. A. A "string-of-beads" vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge. J Virol. 1993 Jan;67(1):348–352. doi: 10.1128/jvi.67.1.348-352.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williamson J. S., Stohlman S. A. Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells. J Virol. 1990 Sep;64(9):4589–4592. doi: 10.1128/jvi.64.9.4589-4592.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yamaguchi K., Goto N., Kyuwa S., Hayami M., Toyoda Y. Protection of mice from a lethal coronavirus infection in the central nervous system by adoptive transfer of virus-specific T cell clones. J Neuroimmunol. 1991 Apr;32(1):1–9. doi: 10.1016/0165-5728(91)90065-F. [DOI] [PMC free article] [PubMed] [Google Scholar]

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