1887

Abstract

The murine coronavirus neurotropic strain JHM (MHV-JHM) nucleocapsid (N) protein induces a strong T-helper cell response in Lewis rats. It has been shown previously that N-specific CD4 T cells can confer protection against acute disease upon transfer to otherwise lethally infected rats. To define the major antigenic regions that elicit this T cell response, truncated fragments of N protein were expressed from a bacterial expression vector and employed as T cell antigens. Lymphocytes from either MHV-JHM-infected or immunized rats were stimulated in culture with virus antigen, grown and tested for their specificity to the N protein fragments. The carboxy-terminally located C4-N fragment (95 amino acids) induced the most pronounced proliferative response irrespective of whether the lymphocyte culture was derived from immunized or MHV-JHM-infected rats. We established T cell lines specific for the truncated N protein fragments and tested their potential to mediate protection by transfer experiments. Only the T cell line C4-N and the T cell line specific for the full-length N protein were protective. By contrast, all truncated N protein fragments elicited a humoral immune response and contained antigenic sites recognized by antibodies from diseased rats.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-74-7-1287
1993-07-01
2022-01-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/74/7/JV0740071287.html?itemId=/content/journal/jgv/10.1099/0022-1317-74-7-1287&mimeType=html&fmt=ahah

References

  1. Bankamp B, Brinckmann U, Reich A, Niewiesk S, ter Meulen V, Liebert UG. 1991; Measles virus nucleocapsid protects rats from encephalitis.. Journal of Virology 65:1695–1700
    [Google Scholar]
  2. Bröker M. 1986; Vectors for regulated high level expression of proteins fused to truncated forms of Escherichia coli β-galactosidase.. Gene Analysis Techniques 3:53–57
    [Google Scholar]
  3. Cheever FS, Daniels JB, Pappenheimer AM, Bailey OD. 1946; murine virus (JF1M) causing disseminated encephalomyelitis with extensive destruction of myelin.. Journal of Experimental Medicine 90:181–194
    [Google Scholar]
  4. Crowl R, Seamans C, Lomedico P, McAndrew S. 1985; Versatile expression in vectors for high-level synthesis of cloned gene productions in Escherichia coli.. Gene 38:31–38
    [Google Scholar]
  5. Dorries R, Schwender S, Imrich H, Harms H. 1991; Population dynamics of lymphocyte subsets in the central nervous system of rats with different susceptibility to coronavirus-induced demyelinating encephalitis.. Immunology 74:539–545
    [Google Scholar]
  6. Flory E, Pfleiderer M, Stuhler A, Wege H. 1993; Induction of protective immunity against coronavirus induced encephalomyelitis: evidence for an important role of CD8+ T cells in vivo.. European Journal of Immunology (in press).
    [Google Scholar]
  7. Giraudon P, Buckland R, Wild TF. 1991; The immune response to measles virus in mice. T-helper response to nucleoprotein and mapping of the T-helper epitopes.. Virus Research 22:41–54
    [Google Scholar]
  8. Koolen MJ, Borst MA, Horzinek MC, Spaan WJ. 1990; Immunogenic peptide comprising a mouse hepatitis virus A59 B-cell epitope and an influenza virus T-cell epitope protects against lethal infection.. Journal of Virology 64:6270–6273
    [Google Scholar]
  9. Körner H, Schliephake A, Winter J, Zimprich F, Lassmann H, Sedgwick J, Siddell S, Wege H. 1991; Nucleocapsid or spike protein-specific CD4+ T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+ T cells.. Journal of Immunology 147:2317–2323
    [Google Scholar]
  10. Kyuwa S, Stohlman SA. 1990; Pathogenesis of a murine coronavirus, strain JHM in the central nervous system of mice.. Seminars in Virology 1:273–280
    [Google Scholar]
  11. Messing J, Groneborn B, Müller-Hill B, Hofschneider PH. 1977; Filamentous coliphage M13 as a cloning vehicle: insertion of a ffindll fragment of the lac regulatory region in M13 replicative form in vitro.. Proceedings of the National Academy of Sciences, U.S.A. 74:3642–3646
    [Google Scholar]
  12. Nagashima K, Wege H, Meyermann R, ter Meulen V. 1978; Coronarvirus induced subacute demyelinating encephalomyelitis in rats. A morphological analysis.. Acta neuropathologica 44:63–70
    [Google Scholar]
  13. Nagashima K, Wege H, Meyermann R, ter Meulen V. 1979; Demyelinating encephalomyelitis induced by a long-term coronavirus infection in rats.. Acta Neuropathologica 45:205–213
    [Google Scholar]
  14. Parker MM, Masters PS. 1990; Sequence comparison of the N genes of five strains of the coronavirus mouse hepatitis virus suggests a three domain structure for the nucleocapsid protein.. Virology 179:463–468
    [Google Scholar]
  15. Oehen S, Waldner H, Kündig T, Hengartner H, Zinkernagel RM. 1992; Antivirally protective cytotoxic T cell memory to lymphocytic choriomeningitis virus is governed by persisting antigen.. Journal of Experimental Medicine 176:1273–1281
    [Google Scholar]
  16. Perlman S, Schelper R, Bolger E, Ries D. 1987; Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody.. Microbial Pathogenesis 2:185–194
    [Google Scholar]
  17. Raabe T. 1987 Biochemische Untersuchungen zur Replikation von Coronaviren University of Würzburg: Diploma thesis;
    [Google Scholar]
  18. Sedgwick JD, MacPhee IAM, Puklavec M. 1989; Isolation of encephalitogenic CD4+ T cell clones in the rat.. Journal of Immunological Methods 121:185–196
    [Google Scholar]
  19. Sorensen O, Percy D, Dales S. 1980; Sorensen, O., Percy, D. & Dales, S. (1980). In vivo and in vitro models of demyelinating diseases. III.. JHM virus infection of rats. Archives of Neurology 37:478–184
    [Google Scholar]
  20. Stitz L, Schmitz C, Binder D, Zinkernagel R, Paoletti E, Becht H. 1990; Characterization and immunological properties of influenza A virus nucleoprotein (NP): cell-associated NP isolated from infected cells or viral NP expressed by vaccinia recombinant virus did not confer protection.. Journal of General Virology 71:1169–1179
    [Google Scholar]
  21. Stohlman SA, Weiner LP. 1981; Chronic central nervous system disease in mice after JHM virus infection.. Neurology 31:38–14
    [Google Scholar]
  22. Stohlman SA, Matsushima GK, Casteel N, Weiner L. 1986; In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection but do not inhibit virus replication.. Journal of Immunology 136:3052–3056
    [Google Scholar]
  23. Stohlman SA, Kyuwa S, Cohen M, Bergmann C, Polo JM, Yeh J, Anthony R, Keck JG. 1992; Mouse hepatitis virus nucleocapsid protein-specific for the carboxy terminus.. Virology 189:217–224
    [Google Scholar]
  24. Vennema H, de Groot GR, Harbour DA, Horzinek MC, Spaan WJ. 1991; Primary structure of the membrane and nucleocapsid protein genes of feline infectious peritonitis virus and immunogenicity of recombinant vaccinia viruses in kittens.. Virology 181:327–335
    [Google Scholar]
  25. Wang FI, de Groot GR, Stohlman SA, Fleming JO. 1990; Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated.. Journal of Neuroimmunology 30:31–41
    [Google Scholar]
  26. Watanabe R, Wege H, Stohlman SA, ter Meulen V. 1983; Adoptive transfer of EAE-like lesions by BMP stimulated lymphocytes from rats with coronavirus-induced demyelinating encephalomyelitis.. Nature, London 305:150–153
    [Google Scholar]
  27. Watanabe R, Wege H, ter Meulen V. 1987; Comparative analysis of coronavirus JHM induced demyelinating encephalomyelitis in Lewis and Brown-Norway rats.. Laboratory Investigation 57:375–384
    [Google Scholar]
  28. Wege H, Wege H, Nagashima K, ter Meulen V. 1979; Structural polypeptides of the murine coronarvirus JHM.. Journal of General Virology 42:37–47
    [Google Scholar]
  29. Wege H, Siddell S, ter Meulen V. 1982; The biology and pathogenesis of coronaviruses.. Current Topics in Microbiology and Immunology 99:165–200
    [Google Scholar]
  30. Wege H, Dörries R, Wege H. 1984a; Hybridoma antibodies to the murine coronavirus JHM: characterization of epitopes on the peplomer protein (E2).. Journal of General Virology 65:1931–1942
    [Google Scholar]
  31. Wege H, Watanabe R, ter Meulen V. 1984b; Relapsing subacute demyelinating encephalomyelitis in rats in the course of coronarvirus JHM infection.. Journal of Neuroimmunology 6:325–336
    [Google Scholar]
  32. Wege H, Winter J, Meyermann R. 1988; The peplomer protein E2 of coronavirus JHM as a determinant of neurovirulence: definition of critical epitopes by variant analysis.. Journal of General Virology 69:87–98
    [Google Scholar]
  33. Williamson JS, Stohlman SA. 1990; Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells.. Journal of Virology 64:4589–4592
    [Google Scholar]
  34. Zimprich F, Winter J, Wege H, Lassmann H. 1991; Coronavirus induced primary demyelination : indications for the involvement of the humoral immune response.. Neuropathology and Applied Neurobiology 17:469–484
    [Google Scholar]
  35. Zurbriggen A, Fujinami RS. 1990; Immunity to viruses.. Current Opinion in Immunology 2:347–352
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-74-7-1287
Loading
/content/journal/jgv/10.1099/0022-1317-74-7-1287
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error