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Viral Evolution and CTL Epitope Stability During JHMV Infection in the Central Nervous System

  • C. C. Bergmann
  • E. Dimacali
  • S. Stohl
  • N. Marten
  • M. M. C. Lai
  • S. A. Stohlman
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 440)

Abstract

The JHM strain of mouse hepatitis virus (JHMV) establishes a persistent infection in the murine central nervous system (CNS) associated with chronic ongoing demyelination in the absence of detectable virus. To distinguish between immune and replication associated mechanisms of persistence, brains from acutely and persistently infected mice were analyzed for viral RNA mutations in the encapsidation sequence (ECS) and regions encoding either the transmembrane domains of the matrix (M) protein or a protective CTL epitope in the nucleocapsid (N) protein. Detection of the ECS to 120 days post infection (p.i.) indicated low levels of replication. The ECS remained stable whereas the fragment encoding the CTL epitope revealed extensive diversity with mutation frequencies in the order of 2.0 per 1000 nts. The M gene also remained stable despite random mutations during the acute phase. Mutations in the N gene were random and not selected for during persistence, with the exception of a single prominent Pro363 to Ser substitution in a region not associated with any known regulatory function or immune response. Mutations within the CTL epitope affecting CTL recognition were found early in responder BALB/c mice (H-2d), but also in non-responder C57BL/6 (H-2b) mice, suggesting that CTL escape variants play no significant role in establishing persistence.

Keywords

Infected Mouse Viral Evolution Mouse Hepatitis Virus Murine Coronavirus C57BLl6 Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Adami, C., Pooley, J., Glomb, J., Stecker, E., Fazal, F., Fleming, J.O., and Baker, S.C., 1995, Evolution of mouse hepatitis virus (MHV) during chronic infection: Quasispecies nature of the persisting MHV RNA, Virol. 209:337.CrossRefGoogle Scholar
  2. Bergmann, C. and Stohlman, S., 1996, Specificity of the Ld restricted CTL response to the mouse hepatitis virus nucleocapsid protein, J. Virol. 70:3252.PubMedGoogle Scholar
  3. Bergmann, C., McMillan, M., and Stohlman, S., 1993, Characterization of the Ld restricted CTL epitope in the mouse hepatitis virus nucleocapsid protein, J. Virol. 67: 7041.PubMedGoogle Scholar
  4. Fleming, J. O., Trousdale, M.D., El-Zaatari, F.A.K., Stohlman S.A., and Weiner L.P., 1986, Pathogenicity of antigenic variants of murine Coronavirus JHM selected with monoclonal antibodies, Virology 58: 869.Google Scholar
  5. Fosmire, J. A., Hwang K. and Makino S., 1992, Identification and characterization of a Coronavirus packaging signal, J. Virol. 66:3522.PubMedGoogle Scholar
  6. Klenerman, P., Phillips, R., and McMichael, A., 1996, Cytotoxic T-cell antagonism in HIV-1, Seminars Virol. 7:31.CrossRefGoogle Scholar
  7. Kyuwa, S., and Stohlman, S.A., 1990, Pathogenesis of a neurotropic murine Coronavirus, strain JHM in the central nervous system of mice, Seminars Virol. 1: 273.Google Scholar
  8. Lai, M., and D. Cavanagh., 1997, Molecular biology of coronaviruses, Adv. Virus Res. In press.Google Scholar
  9. Pewe, L., Wu, G.F., Barnett, E.M., Castro, R.F., and Perlman S., 1996, Cytotoxic T cell-resistant variants are selected in a virus-induced demyelinating disease. Immunity 5:253.PubMedCrossRefGoogle Scholar
  10. Pfleiderer, M., Skinner, M.A., and Siddell, S.K., 1986, Coronavirus MHV-JHM: nucleotide sequence of the mRNA that encodes the membrane protein, Nucl. Acids Res. 14:6338.PubMedCrossRefGoogle Scholar
  11. Rottier, P. J., Welling, G. E., Welling-Webster, S., Niesters, H. G., Lenstra, J. A., and van der Zeijst, B.A.M., 1986, Predicted membrane topology of the Coronavirus protein E1, Biochem. 25: 1335.CrossRefGoogle Scholar
  12. Rowe, C.L., Baker, S.C., N.M.J., and Fleming, J.O., 1997, Evolution of mouse hepatitis virus: Detection and characterization of spike deletion variants during persistent infection, J. Virol. 71:2959.PubMedGoogle Scholar
  13. Skinner, M.A., and Sidell, S.G., 1983, Coronavirus JHM: nucleotide sequence of the mRNA that encodes nucleocapsid protein, Nucl. Acids Res. 11:5045.PubMedCrossRefGoogle Scholar
  14. Stohlman, S.A., Bergmann, C., van der Veen, R., and Hinton, D., 1995, Mouse hepatitis virus-specific cytotoxic T lymphocytes protect from lethal infection without eliminating virus from the central nervous sytem, J. Virol. 69:684.PubMedGoogle Scholar
  15. Stohlman, S. A., Brayton P.R., Fleming, J.O., Weiner, L.P. and Lai, M.M.C., 1982, Murine coronaviruses: isolation and characterization of two plaque morphology variants of the JHM neurotropic strain, J. Gen. Virol. 63:265.PubMedCrossRefGoogle Scholar
  16. Stohlman, S.A., Fleming, J.O., Patton, C.D., and Lai, M.M.C., 1983, Synthesis and subcellular localization of the murine Coronavirus nucleocapsid protein, Virology 130:527.PubMedCrossRefGoogle Scholar
  17. Williamson, J.S.P., and Stohlman S.A.S., 1990, Effective clearance of mouse hepatitis virus from the CNS requires both CD4+ and CD8+ T cells, J. Virol. 64:4590.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • C. C. Bergmann
    • 1
    • 2
  • E. Dimacali
    • 1
  • S. Stohl
    • 1
  • N. Marten
    • 1
  • M. M. C. Lai
    • 2
    • 3
  • S. A. Stohlman
    • 1
    • 2
  1. 1.Department of NeurologyUniversity of Southern California School of MedicineLos AngelesUSA
  2. 2.Microbiology and ImmunologyUniversity of Southern California School of MedicineLos AngelesUSA
  3. 3.Howard Hughes Medical InstitutesUniversity of Southern California School of MedicineLos AngelesUSA

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