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Intranuclear inclusions in paramyxovirus-induced encephalitis: evidence for altered nuclear body differentiation

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Summary

Intranuclear inclusion bodies (INB) are frequently encountered in viral infections, where they are thought to be accumulations of viral particles. However, for RNA viruses replicating in the cytoplasm, this compartmentalization represents a paradox not consistent with the viral replication cycle. To define the basis for intranuclear paramyxoviral inclusion bodies in astrocytes, natural cases of canine distemper virus subacute encephalitis were examined by light and transmission electron microscopy, and by quantitative confocal immunofluorescene microscopy. Although INB were viral antigen positive, they were not composed of structurally recognizable paramyxoviral nucleocapsids. The structural basis for the INB was instead viral antigen-associated forms of nucleolar development known as nuclear bodies. Three variants of the light microscopic Cowdry type A INB were complex nuclear bodies, giant beaded nuclear bodies (sphaeridia), and nuclear body-associated granulofilamentous matrices. In the latter, the granulofilamentous matrix frequently filled the nucleus, resulting in a fourth morphological INB variant, and was associated with morphological evidence of nuclear degeneration. These findings suggest a novel mechanism of virus-induced cytopathology whereby intranuclear viral protein exerts deleterious effects upon nucleolar differentiation in infected cells and hence altered host cell RNA metabolism.

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References

  1. Axthelm MK (1985) Immunocytochemical methods for demonstrating canine distemper virus antigen in aldehydefixed paraffin-embedded tissue. J Virol Methods 13:215–230

    Google Scholar 

  2. Baker SC, Moyer SA (1988) Encapsidation of Sendai virus genome RNAs by purified NP protein during in vitro replication. J Virol 62:834–838

    Google Scholar 

  3. Bohn W, Ciampor F, Rutter R, Mannweiler K (1990) Localization of nucleocapsid polypeptides in measles virus-infected cells by immunogold labelling after resin embedding. Arch Virol 114:53–64

    Google Scholar 

  4. Bouteille M, Kalifat SR, Delarue J (1967) Ultrastructural variations of nuclear bodies in human diseases. J Ultrastruct Res 19:474–486

    Google Scholar 

  5. Chaly N, Setterfield G, Kaplan JG, Brown DL (1983) Nuclear bodies in mouse splenic lymphocytes. II. Cytochemistry and autoradiography during stimulation by concanavalin A. Biol Cell 49:35–43

    Google Scholar 

  6. Chander P, Soni A, Suri A, Bhagwat R, Yoo J, Treser G (1987) Renal ultrastructural markers in AIDS-associated nephropathy. Am J Pathol 126:513–526

    Google Scholar 

  7. Chui LW-L, Vainionpää R, Marusyk R, Salmi A, Norrby E (1986) Nuclear accumulation of measles virus nucleoprotein associated with a temperature sensitive mutant. J Gen Virol 67:2153–2161

    Google Scholar 

  8. Cook RD, Wisniewski HM (1973) The role of oligodendroglia and astroglia in Wallerian degeneration of the optic nerve. Brain Res 61:191–206

    Google Scholar 

  9. Cowdry EV (1934) The problem of intranuclear inclusions in virus diseases. Arch Pathol 18:527–542

    Google Scholar 

  10. D'Agati V, Suh J-J, Carbone L, Cheng J-T, Appel G (1989) Pathology of HIV-associated nephropathy: a detailed morphologic and comparative study. Kidney Int 35:1358–1370

    Google Scholar 

  11. Dumont A, Roberts A (1971) Ultrastructure of complex nuclear bodies produced experimentally in hamster peritoneal macrophages. J Ultrastruct Res 36:483–492

    Google Scholar 

  12. Dupy-Coin AM, Bouteille M (1992) Developmental pathway of granular and beaded nuclear bodies from nucleoli. J Ultrastruct Res 40:55–67

    Google Scholar 

  13. Dworetzky SI, Feldherr CM (1988) Translocation of RNA-coated gold particles through the nuclear pores of oocytes. J Cell Biol 106:575–584

    Google Scholar 

  14. Eng LF (1988) Regulation of glial intermediate filaments in astrogliosis. In: Norenberg MD, Hertz L, Schousboe A (eds) Neurology and Neurobiology, vol 39. Alan R. Liss, New York, pp 79–90

    Google Scholar 

  15. Giulian D, Lachman LB (1985) Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 228:497–499

    Google Scholar 

  16. Granboulan N, Tournier P, Wicker R, Bernhard W (1963) An electron microscope study of the development of SV40 virus. J Cell Biol 17:423–441

    Google Scholar 

  17. Hamaguchi M, Nishikawa K, Toyoda T, Yoshida T, Hanaichi T, Nagai Y (1985) Transcriptive complex of Newcastle disease virus. II. Structural and functional assembly associated with the cytoskeletal framework. Virology 147:295–308

    Google Scholar 

  18. Hart L, Donovan RM, Goldstein E, Brady FP (1990) Detection of human immunodeficiency virus in infected CEM cells using fluorescent DNA probes and a laser-based computerized image cytofluorometry system. Anal Quant Cytol Histol 12:127–134

    Google Scholar 

  19. Hatten ME (1980) Neuronal inhibition of astroglia cell proliferation is membrane-mediated. J Cell Biol 104:1353–1360

    Google Scholar 

  20. Hernandez-Verdun D, Prevot S, Andre C, Guilly MN, Masson C, Wolfe J (1988) Autoimmune serum containing an antibody against a 94-kDa nucleolar protein. Biol Cell 64: 331–341

    Google Scholar 

  21. Kingsbury DW, Hsu H, Murti KG (1978) Intracellular metabolism of Sendai virus nucleocapsids. Virology 91:86–94

    Google Scholar 

  22. Koestner A, Long JF (1970) Ultrastructure of canine distemper virus in explant tissue cultures of canine cerebellum. Lab Invest 23:196–201

    Google Scholar 

  23. Kohorn EI, Rice SI, Hemperly S, Gordon M (1972) The relation of the structure of progestational steroids to nucleolar differentiation in human endometrium. J Clin Endocrinol Metab 34:257–264

    Google Scholar 

  24. Krakowka S, Axthelm MK, Gorham JR (1987) Effects of induced thrombocytopenia on viral invasion of the central nervous system in canine distemper virus infection. J Comp Pathol 97:441–450

    Google Scholar 

  25. Kubota S, Nosaka T, Cullen BR, Makai M, Hatanaka M (1991) Effects of chimeric mutants of human immunodeficiency virus type I Rev and human T cell leukemia virus type I Rex on nucleolar targeting signals. J Virol 65:2452–2456

    Google Scholar 

  26. Kuhn C (1967) Nuclear bodies and intranuclear globulin inclusions in Waldenström's macroglobulinemia. Lab Invest 17:404–415

    Google Scholar 

  27. Lafarga M, Villegas J, Crespo D (1985) Changes in nucleolar morphology and volume in the supraoptic nucleus neurons during postnatal development of the rat. Dev Brain Res 22:310–313

    Google Scholar 

  28. Lafarga M, Berciano MT, Suarez I, Viadero CF, Andres MA, Berciano J (1991) Cytology and organization of reactive astroglia in human cerebellar cortex with severe loss of granule cells: a study on the ataxic form of Creutzfeldt-Jacob disease. Neuroscience 40:337–352

    Google Scholar 

  29. Moyer SA, Smallwood-Kentro S, Haddad A, Prevec L (1991) Assembly and transcription of synthetic vesicular stomatitis virus nucleocapsids. J Virol 65:2170–2178

    Google Scholar 

  30. Murti KG, Davis DS, Kitchingman GR (1990) Localization of adenovirus-encoded DNA replication proteins in the nucleus by immunogold electron microscopy. J Gen Virol 71:2847–2857

    Google Scholar 

  31. Nistal M, Regadera J, Paniagua R, Rodríguez MC (1990) Nuclear bodies (sphaeridia) in Sertoli cells of a man with acquired immunodeficiency syndrome (AIDS) and testicular infection with cytomegalovirus. Ultrastruct Pathol 14:21–26

    Google Scholar 

  32. Oglesbee M, Jackwood D, Perrine K, Axthelm M, Krakowka S, Rice J (1986) In vitro detection of canine distemper virus nucleic acid with a virus-specific cDNA probe by dot-blot and in situ hybridization. J Virol Methods 14:195–211

    Google Scholar 

  33. Oglesbee MJ, Tatalick L, Ringler S, Rice J, Krakowka S (1989) Rapid isolation of morbillivirus nucleocapsid for genomic RNA cDNA cloning and the production of specific core protein antisera. J Virol Methods 24:285–300

    Google Scholar 

  34. O'Shea JD, Studdert MJ (1978) Growth of an autonomously replicating parvovirus (feline panleukopenia): kinetics and morphogenesis. Arch Virol 57:107–122

    Google Scholar 

  35. Oyanagi S, ter Meulen V, Müller D, Katz M, Koprowski H (1970) Electron microscopic observations in subacute sclerosing panencephalitis brain cell cultures: their correlation with cytochemical and immunocytological findings. J Virol 6:370–379

    Google Scholar 

  36. Oyanagi S, Rorke LB, Katz M, Koprowski H (1971) Histopathology and electron microscopy of three cases of subacute sclerosing panencephalitis. Acta Neuropathol (Berl) 18:58–73

    Google Scholar 

  37. Padykula HA, Pockwinse SM (1983) Uterine simple and complex nuclear bodies are separate structural entities. Anat Rec 205:119–130

    Google Scholar 

  38. Patrizi G, Middelkamp JN (1969) In vivo and in vitro demonstration of nuclear bodies in vaccinia infected cells. J Ultrastruct Res 28:275–287

    Google Scholar 

  39. Radoux D, Goessens G, Simar LJ (1984) Nuclear bodies in mouse lymphoid cells stimulated by lipopolysaccharide. Eur J Cell Biol 34:193–205

    Google Scholar 

  40. Raine CS, Feldman LA, Sheppard RD, Bornstein MB (1969) Ultrastructure of measles virus in cultures of hamster cerebellum. J Virol 4:169–181

    Google Scholar 

  41. Rue G, Bierne J (1988) Structural and functional relationships between nuclear bodies and the nucleolus-DNA body complex in the oocyte of Amphiporous lactifloreus. Cell Differ Dev 25:11–22

    Google Scholar 

  42. Ryder DR, Horvath E, Kovacs K (1979) Nuclear inclusions in the human adenohypophysis. Acta Anat (Basel) 105:273–283

    Google Scholar 

  43. Simard R (1966) Specific nuclear and nucleolar ultrastructural lesions induced by proflavin and similarly acting antimetabolites in tissue culture. Cancer Res 26:2316–2328

    Google Scholar 

  44. Spehner D, Kirn A, Drillien R (1992) Assembly of nucleocapsid-like structures in animal cells infected with a vaccinia virus recombinant encoding the measles virus nucleoprotein. J Virol 65:6296–6300

    Google Scholar 

  45. Vagner-Copadano A-M, Mauchamp J, Stahl A, Lissitzky S (1980) Nucleolar budding and formation of nuclear bodies in cultured thyroid cells stimulated by thyrotropin, dibutyryl cyclic AMP, and prostaglandin E2. J Ultrastruct Res 70:37–51

    Google Scholar 

  46. Warren JT, McMahon JB, Weislow OS, Gulakowski RJ, Kiser RF, Boyd MR (1990) Interactive laser cytometric analysis of retroviral protein expression in HIV-infected lymphocytic cell lines. AIDS Res Hum Retroviruses 6:1131–1137

    Google Scholar 

  47. Wiśniewski H, Raine CS, Kay WJ (1972) Observations on viral demyelinating encephalomyelitis. Canine distemper. Lab Invest 26:589–599

    Google Scholar 

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  1. The Department of Veterinary Pathobiology, The Ohio State University, 1925 Coffey Road, 43210, Columbus, OH, USA

    M. Oglesbee

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Supported by The State of Ohio Canine Research Fund

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Oglesbee, M. Intranuclear inclusions in paramyxovirus-induced encephalitis: evidence for altered nuclear body differentiation. Acta Neuropathol 84, 407–415 (1992). https://doi.org/10.1007/BF00227668

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  • DOI: https://doi.org/10.1007/BF00227668

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