Skip to main content
Log in

Immunoenzymatic labelling of JC papovavirus T antigen in brains of patients with progressive multifocal leukoencephalopathy

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Formalin-fixed, paraffin-embedded autopsy sections of brains from two patients with progressive multifocal leukoencephalopathy (PML) were stained by peroxidase-antiperoxidase methods for human papovavirus T antigen, a nonstructural protein expressed in cells lytically infected or transformed by JC, BK, and SV40 viruses. Adjacent sections were stained for papovavirus common structural antigen, a component of JC, BK, and SV40 virions which is synthesized in productively infected but not transformed cells. Intense immunoperoxidase labelling specific for T antigen was detected in large numbers of oligodendrocytes at the edges of demyelinated areas and in occasional oligodendrocytes within otherwise normal brain. Occasional morphologically normal astrocytic cells exhibited similar specific staining, but only rate atypical astrocytic cells contained detectable amounts of T antigen. Examination of adjacent sections stained with antisera to common structural antigen revealed an identical pattern of immunoenzymatic labelling, indicating that most of the cells expressing T antigen were also expressing viral structural proteins. The present study demonstrates that T antigen can be identified by immunoperoxidase methods in routinely processed autopsy material from cases of PML, but that detectable amounts of antigen are found almost exclusively in cells undergoing lytic infection.

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

  • Aksamit AJ, Mourrain P, Sever JL, Major EO (1985) Progressive multifocal leukoencephalopathy: investigation of three cases using in situ hybridization with JC virus biotinylated DNA probe. Ann Neurol 18:490–496

    Google Scholar 

  • Becker, LE, Narayan O, Johnson RT (1976) Studies of human papovavirus tumor antigen in experimental and human cerebral neoplasms. Can J Neurol Sci 3:105–109

    Google Scholar 

  • Budka H, Shah KV (1983) Papovavirus antigens in paraffin sections of PML brains. In: Sever JL, Madden DL (eds) Polyomaviruses and human neurological disease. Alan R Liss, New York, pp 299–309

    Google Scholar 

  • Costa J, Howley PM, Bowling MC, Howard R, Bauer WC (1981) Presence of human papilloma viral antigens in juvenile multiple laryngeal papilloma. Am J Clin Pathol 75:194–197

    Google Scholar 

  • Dorries K, Johnson RT, terMeulen V (1979) Detection of polyomavirus DNA in PML-brain tissue by in situ hybridization. J Gen Virol 42:49–57

    Google Scholar 

  • Dougherty RM (1976) A comparison of human papovavirus T antigens. J Gen Virol 33:61–70

    Google Scholar 

  • Gerber MA, Shah KV, Thung SN, ZuRhein GM (1980) Immunohistochemical demonstration of common antigen of polyomaviruses in routine histologic tissue sections of animals and man. Am J Clin Pathol 73:794–797

    Google Scholar 

  • Greenlee JE, Narayan O, Johnson RT, Herndon RM (1977) Induction of brain tumors in hamsters with BK virus, a human papovavirus. Lab Invest 36:636–641

    Google Scholar 

  • Ho K, Garancis JC, Paegle RD, Gerber MA, Borkowski WJ (1980) Progressive multifocal leukoencephalopathy and malignant lymphoma of the brain in a patient with immunosuppressive therapy. Acta Neuropathol (Berl) 52:81–83

    Google Scholar 

  • Itoyama Y, Webster HD, Sternberger NH, Richardson EP, Walker DL, Quarles RH, Padgett BL (1982) Distribution of papovavirus, myelin-associated glycoprotein, and myelin basis protein in progressive multifocal leukoencephalopathy lesion. Ann Neurol 11:396–407

    Google Scholar 

  • Jarvis DL, Lanford RE, Butel JS (1984) Structural comparisons of wild-type and nuclear transport-defective simian virus 40 large Tumor antigens. Virology 134:168–176

    Google Scholar 

  • Johnson RT (1982) Chronic inflammatory and demyelinating diseases. In: Johnson RT (ed) Viral infections of the nervous system. Raven Press, New York, pp 255–263

    Google Scholar 

  • Lanford RE, Butel JS (1979) Antigenic relationship of SV40 early proteins to purified large T polypeptide. Virology 97:295–306

    Google Scholar 

  • Lanford RE, Butel JS (1980a) Inhibition of nuclear migration of wild-type SV40 tumor antigen by a transport-defective mutant of SV40-adenovirus 7 hybrid virus. Virology 105:303–313

    Google Scholar 

  • Lanford RE, Butel JS (1980b) Biochemical characterization of nuclear and cytoplasmic forms of SV40 tumor antigens encoded by parental and transport-defective mutant SV40-adenovirus 7 hybrid viruses. Virology 105:314–327

    Google Scholar 

  • Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ (1971) Cultivation of a papovavirus-like virus from human brain with progressive multifocal leukoencephalopathy. Lancet 1:1257–1260

    Google Scholar 

  • Rapp F, Melnick JL, Butel JS, Kitahara T (1964) The incorporation of SV40 genetic material into adenovirus 7 as measured by intranuclear synthesis of SV40 tumor antigen. Proc Natl Acad Sci USA 52:1348–1352

    Google Scholar 

  • Rigby PW, Lane DP (1983) Stucture and function of simian virus 40 large T-antigen. In: Klein G (ed) Advances in viral oncology, vol 3. Raven Press, New York, pp 31–57

    Google Scholar 

  • Shah KV, Ozer HL, Ghazey HN, Kelly TJ (1977) Common structural antigen of papovaviruses of the simian virus 40-polyoma subgroup. J Virol 21:179–186

    Google Scholar 

  • Stenman S, Zeuthen J, Ringertz NR (1975) Expression of SV40 T antigen during the cell cycle of SV40-transformed cells. Int J Cancer 15:547–554

    Google Scholar 

  • Swetly P, Watanabe Y (1974) Cell cycle-dependent transcription of SV40 DNA in SV40-transformed cells. Biochemistry 13:4122–4126

    Google Scholar 

  • ZuRhein GM (1969) Association of papova-virions with a human demyelinating disease (progressive multifocal leukoencephalopathy). Prog Med Virol 11:185–247

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by UPHS-NINCDS research award RO1-NS-13982

Rights and permissions

Reprints and permissions

About this article

Cite this article

Greenlee, J.E., Keeney, P.M. Immunoenzymatic labelling of JC papovavirus T antigen in brains of patients with progressive multifocal leukoencephalopathy. Acta Neuropathol 71, 150–153 (1986). https://doi.org/10.1007/BF00687977

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00687977

Key words

Navigation