Skip to main content
Log in

Measles virus matrix protein gene expression in a subacute sclerosing panencephalitis patient brain and virus isolate demonstrated by cDNA hybridization and immunocytochemistry

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Subacute sclerosing panencephalitis (SSPE) is a rare, fatal disease of children caused by a persistent measles virus infection of the central nervous system. A defect in synthesis of measles virus matrix (M) protein may be a factor in virus persistence in the brain. This study details attempts to detect expression of M protein in the brain of an SSPE patient, in the cell-associated virus isolated from this brain, and in brains of ferrets inoculated with the isolate. In situ hybridization with a tritiated cloned cDNA probe was used to search for RNA encoding M protein. Immunostaining with monospecific antiserum and the avidin-biotin-peroxidase technique was done to locate the polypeptide. The data obtained indicate that although nucleotide sequences coding for M protein were detected in the patient and ferret brains, expression of M protein in these tissues could not be detected. In the cultured SSPE virus isolate, the results were the same until the infected cells were examined by electron microscopy and a very limited expression of M protein was revealed. This suggests either diminished synthesis and/or rapid degradation of M protein in this cell-associated virus strain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Baczko K, Liebert UG, Billeter M, Cattaneo R, Budka H, ter Meulen V (1986) Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis. J Virol 59: 472–478

    Google Scholar 

  2. Brown HR, Thormar H (1976) A non-productive subacute sclerosing panencephalitis (SSPE) virus of human and ferret. An ultrastructural study. Acta Neuropathol (Berl) 34: 339–351

    Google Scholar 

  3. Brown HR, Thormar H, Barshatzky M, Wisniewski HM (1985) Localization of measles virus antigens in subacute sclerosing panencephalitis in ferrets. Lab Anim Sci 35: 233–237

    Google Scholar 

  4. Brown HR, Goller N, Thormar H, Norrby E (1987) Fuzzy material surrounding measles virus nucleocapsids identified as matrix protein. Arch Virol 94: 163–168

    Google Scholar 

  5. Carter MJ, Willcocks MM, ter Meulen V (1983) Defective translation of measles virus matrix protein in a subacute sclerosing panencephalitis cell line. Nature 305: 153–155

    Google Scholar 

  6. Cattaneo R, Schmid A, Rebmann G, Baczko K, ter Meulen V, Bellini WJ, Rozenblatt S, Billeter MA (1986) Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: interrupted matrix protein reading frame and transcription alteration. Virology 154: 97–107

    Google Scholar 

  7. Fournier JG, Rozenblatt S, Bouteille M (1983) Localization of measles virus nucleic acid sequences in infected cells by in situ hybridization. Biol Cell 49: 287–290

    Google Scholar 

  8. Fournier JG, Tardieu M, Lebon P, Robain O, Ponsot G, Rozenblatt S, Bouteille M (1985) Detection of measles virus RNA in lymphocytes from peripheral-blood and brain perivascular infiltrates of patients with subacute sclerosing panencephalitis. N Engl J Med 313: 910–915

    Google Scholar 

  9. Gorecki M, Rozenblatt S (1980) Cloning of DNA complementary to the measles virus mRNA encoding nucleocapsid protein. Proc Natl Acad Sci USA 77: 3686–3690

    Google Scholar 

  10. Haase AT, Brahic M, Stowring L, Blum H (1984) Detection of viral nucleic acids by in situ hybridization. Methods Virol 7: 189–226

    Google Scholar 

  11. Haase AT, Gantz D, Eble B, Walker D, Stowring L, Ventura P, Blum H, Wietgrefe S, Zupancic M, Tourtellotte W, Gibbs CJ, Norrby E, Rozenblatt S (1985) Natural history of restricted synthesis and expression of measles virus genes in subacute sclerosing panencephalitis. Proc Natl Acad Sci USA 82: 3020–3024

    Google Scholar 

  12. Hall WW, Choppin PW (1981) Measles virus proteins in the brain tissue of patients with SSPE. N Engl J Med 304: 1151–1155

    Google Scholar 

  13. Hall WW, Lamb RA, Choppin PW (1979) Measles and SSPE virus proteins: lack of antibodies to the M protein in patients with SSPE. Proc Natl Acad Sci USA 76: 2047–2051

    Google Scholar 

  14. Huang WM, Gibson SJ, Facer P, Gu J, Polak JM (1983) Improved section adhesion for immunocytochemistry using high molecular weight polymers ofl-lysine as a slide coat. Histochemistry 77: 275–279

    Google Scholar 

  15. Johnson KP, Norrby E, Swoveland P, Carrigan DR (1981) Experimental subacute sclerosing panencephalitis: selective disappearance of measles virus matrix protein from the central nervous system. J Infect Dis 144: 161–169

    Google Scholar 

  16. Liebert UG, Baczko K, Budka H, ter Meulen V (1986) Restricted expression of measles virus proteins in brains from cases of subacute sclerosing panencephalitis. J Gen Virol 67: 2435–2444

    Google Scholar 

  17. Lin FH, Thormar H (1980) Absence of M protein in a cell associated subacute sclerosing panencephalitis virus. Nature 285: 490–492

    Google Scholar 

  18. McLean IW, Nakane PK (1974) Periodate-lysine paraformaldehyde fixative: a new fixative for immunoelectron microscopy. J Histochem Cytochem 22: 1077–1083

    Google Scholar 

  19. Norrby E, Kristensson K, Brzosko WJ, Kapsenberg JG (1985) Measles virus matrix protein detected by immune fluorescence with monoclonal antibodies in the brain of patients with subacute sclerosing panencephalitis. J Virol 56: 337–340

    Google Scholar 

  20. Shapshak P, Tourtellotte WW, Nakamura S, Graves MC, Darvish M, Hoffman D, Walsh MJ, Fareed GC, Schmid P, Heinzmann C, Sidhu K, Bedows E, Rozenblatt S, Berry K, Hawkins S (1985) Subacute sclerosing panencephalitis: measles virus matrix protein nucleic acid sequences detected by in situ hybridization. Neurology 35: 1605–1609

    Google Scholar 

  21. Sheppard RD, Raine CS, Bornstein MB, Udem SA (1985) Measles virus matrix protein synthesized in a subacute sclerosing panencephalitis cell line. Science 228: 1219–1221

    Google Scholar 

  22. Sheppard RD, Raine CS, Bornstein MB, Udem SA (1986) Rapid degradation restricts measles virus matrix protein expression in a subacute sclerosing panencephalitis cell line. Proc Natl Acad Sci USA 83: 7913–7917

    Google Scholar 

  23. Thormar H, Jervis GA, Karl SC, Brown HR (1973) Passage in ferrets of encephalitogenic cell-associated measles virus isolated from brain of a patient with subacute sclerosing panencephalitis. J Infect Dis 127: 678–685

    Google Scholar 

  24. Thormar H, Arnesen K, Mehta PD (1977) Encephalitis in ferrets caused by a non-productive strain of measles virus (D. R.) isolated from a patient with subacute slcerosing panencephalitis (SSPE). J Infect Dis 136: 229–237

    Google Scholar 

  25. Varsanyi TM, Utter G, Norrby E (1984) Purification, morphology and antigenic characterization of measles virus envelope components. J Gen Virol 65: 355–366

    Google Scholar 

  26. Wechsler SL, Weiner HL, Fields BN (1979) Immune response in SSPE: reduced antibody response to the matrix protein of measles virus. J Immunol 123: 884–889

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This paper is dedicated to the late Dr. George A. Jervis, first Director of the Institute for Basic Research, Physician and Scientist, for his humanity and many contributions to the mentally retarded and developmentally disabled.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, H.R., Goller, N.L., Thormar, H. et al. Measles virus matrix protein gene expression in a subacute sclerosing panencephalitis patient brain and virus isolate demonstrated by cDNA hybridization and immunocytochemistry. Acta Neuropathol 75, 123–130 (1987). https://doi.org/10.1007/BF00687072

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00687072

Key words

Navigation