Skip to main content
Log in

Expression of viral antigens in the central nervous system of visna-infected sheep: an immunohistochemical study on experimentsl visna induced by virus strains of increased neurovirulence

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

Summary

Icelandic sheep were infected by intracerebral inoculation with visna virus strains of increased neurovirulence. The character and severity of pathological lesions were studied in brains from four sheep that developed clinical signs 5 to 12 weeks after infection. Viral antigens were identified by immunostaining using mouse monoclonal antibodies against two core proteins and the Avidin-Biotin method of detection. The pathological lesions were in general more severe than observed following infection with the parent strain K1514. Primary demyelination, a late manifestation of infection with K1514, was detected. Thus, in addition to causing more severe pathological lesions, these neurovirulent strains apparently have an increased potential to induce primary demyelination. Viral antigens were detected in lymphocytes, plasma cells, macrophages, endothelial cells, pericytes, fibroblasts and choroidal epithelial cells. Neurons and glial cells were antigen negative. The spectrum of infected cells in the brain was similar to that observed in infections with human immunodeficiency virus. These results do not support the view that the demyelination is caused by immunological damage to infected oligodendrocytes. A perturbation of the function of oligodendrocytes through a non-productive infection could be the underlying pathogenetic mechanism and/or a non-specific demyelination due to the intense inflammatory reaction.

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. Braun MJ, Clements JE, Gonda MA (1987) The visna virus genome: evidence for a hypervariable site in theenv gene and sequence homology among lentivirus envelope proteins. J Virol 61:4046–4054

    Google Scholar 

  2. Buchmeier MJ, Lewicki HA, Talbot PJ, Knobler RL (1984) Murine hepatitis virus-4 (Strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology 132:261–270

    Google Scholar 

  3. Budka H (1986) Multinucleated giant cells in brain: a hallmark of acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 69:253–258

    Google Scholar 

  4. Clements JE, D'Antonio N, Narayan O (1982) Genomic changes associated with antigenic variation of visna virus. J Mol Biol 158:415–434

    Google Scholar 

  5. Dalziel RG, Lampert PW, Talbot PJ, Buchmeier MJ (1986) Site-specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence. J Virol 59:463–471

    Google Scholar 

  6. Gartner S, Markovitz P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219

    Google Scholar 

  7. Gendelman HE, Narayan O, Molineaux S, Clements JE, Ghotbi Z (1985) Slow persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow. Proc Natl Acad Sci USA 82:7086–7090

    Google Scholar 

  8. Georgsson G, Nathanson N, Pálsson PA, Pétursson G (1976) The pathology of visna and maedi in sheep. In: Kimberlin RH (ed) Slow virus diseases of animals and man. North Holland, Amsterdam, pp 61–96

    Google Scholar 

  9. Georgsson G, Pálsson PA, Panitch H, Nathanson N, Pétursson G (1977) Ultrastructure of early visna lesions. Acta Neuropathol (Berl) 37:127–135

    Google Scholar 

  10. Georgsson G, Martin JR, Klein J, Pálsson PA, Nathanson N, Pétursson G (1982) Primary demyelination in visna. An ultrastructural study of Icelandic sheep with clinical signs following experimental infection. Acta Neuropathol (Berl) 57:171–178

    Google Scholar 

  11. Gonda MA, Wong-Staal F, Gallo RC, Clements JE, Narayan O, Gilden RV (1985) Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science 227:173–177

    Google Scholar 

  12. Haase AT (1985) Pathogenesis of lentivirus infections. Nature 322:130–136

    Google Scholar 

  13. Haase AT, Stowring L, Narayan O, Griffin D, Price D (1977) Slow persistent infection caused by visna virus: role of host restriction. Science 195:175–177

    Google Scholar 

  14. Harter DH, Choppin PW (1967) Cell-fusing activity of visna virus particles. Virology 31:279–288

    Google Scholar 

  15. Houwers DJ, Schaake J (1987) An improved ELISA for the detection of antibodies to ovine and caprine lentiviruses, employing monoclonal antibodies in a one-step assay. J Immunol Methods 98:151–154

    Google Scholar 

  16. Kennedy PGE, Narayan O, Ghotbi Z, Hopkins J, Gendelman HE, Clements JE (1985) Persistent expression of Ia antigen and viral genome in visna-maedi virus-induced inflammatory cells. J Exp Med 162:1970–1982

    Google Scholar 

  17. Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV, Chen ISY (1987) Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 236:819–822

    Google Scholar 

  18. Lairmore MD, Akita GY, Russell HI, DeMartini JC (1987) Replication and cytopathic effects of ovine lentivirus strains in alveolar macrophages correlate with in vivo pathogenicity. J Virol 61:4038–4042

    Google Scholar 

  19. Lumsden CE (1970) The neuropathology of multiple sclerosis. Handb Clin Neurol 9:217–309

    Google Scholar 

  20. Lutley R, Pétursson G, Georgsson G, Pálsson PA, Nathanson N (1985) Strains of visna virus with increased neurovirulence. In: Sharp JM, Hoff-Jörgensen R (eds) Slow viruses in sheep, goats and cattle. Commission of the European Communities, Luxembourg, pp 45–49

    Google Scholar 

  21. Narayan O, Wolinski JS, Clements JE, Strandberg JD, Griffin DE, Cork LC (1982) Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats. J Gen Virol 59:345–356

    Google Scholar 

  22. Narayan O, Strandberg JD, Griffin DE, Clements JE, Adams RJ (1983) Aspects of the pathogenesis of visna in sheep. In: Mims CA, Cuzner ML, Kelly RE (eds) Viruses and demyelinating diseases. Academic Press, London, pp 125–140

    Google Scholar 

  23. Narayan O, Scheffer D, Clements JE, Tennekoon G (1985) Restricted replication of lentiviruses. Visna viruses induce a unique interferon during interaction between lymphocytes and infected macrophages. J Exp Med 162:1954–1969

    Google Scholar 

  24. Nathanson N, Panitch H, Pálsson PA, Pétursson G, Georgsson G (1976) Pathogenesis of visna. II. Effect of immunosuppression upon early central nervous system lesions. Lab Invest 35:444–451

    Google Scholar 

  25. Nathanson N, Martin JR, Georgsson G, Pálsson PA, Lutley R, Pétursson G (1981) Effect of post-infection immunization on the severity of experimental visna. J Comp Pathol 91:185–191

    Google Scholar 

  26. Panitch H, Pétursson G, Georgsson G, Pálsson PA, Nathanson N (1976) Pathogenesis of visna. IV. Immune responses to central nervous system antigens in visna and experimental allergic encephalomyelitis. Lab Invest 35:452–460

    Google Scholar 

  27. Pétursson G, Nathanson N, Georgsson G, Panitch H, Pálsson PA (1976) Pathogenesis of visna. I. Sequential virologic, serologic and pathologic studies. Lab Invest 35:402–412

    Google Scholar 

  28. Pétursson G, Martin JR, Georgsson G, Nathanson N, Pálsson PA (1979) Visna. The biology of the agent and the disease. In: Tyrrel DAJ (ed) New perspectives in clinical microbiology, vol 2. Aspects of slow and persistent infections. Nijhoff, The Hague, pp 198–220

    Google Scholar 

  29. Prineas J (1975) Pathology of the early lesion in multiple sclerosis. Hum Pathol 6:531–554

    Google Scholar 

  30. Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–592

    Google Scholar 

  31. Pumarola-Sune T, Navia BA, Cordon-Cardo MD, Cho E-S, Price RW (1987) HIV antigen in brains of patients with AIDS dementia complex. Ann Neurol 21:490–496

    Google Scholar 

  32. Sharer LR, Cho E-S, Epstein LG (1985) Multinucleated giant cells and HTLV-III in AIDS encephalopathy. Hum Pathol 16:760

    Google Scholar 

  33. Sigurdsson B, Thormar H, Pálsson PA (1960) Cultivation of visna virus in tissue culture. Arch Gesamte Virusforsch 10:368–381

    Google Scholar 

  34. Sonigo P, Alizon M, Staskus K, Klatzman D, Cole S, Danos O, Retzel E, Thioallais P, Haase A, Wain-Hobson S (1985) Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell 42:369–382

    Google Scholar 

  35. Stanley J, Bhaduri LM, Narayan O, Clements JE (1987) Topographical rearrangements of visna virus envelope glycoprotein during antigenic drift. J Virol 61:1019–1028

    Google Scholar 

  36. Stoler MH, Eskin TA, Benn S, Angerer RC, Angerer LM (1986) Human T-cell lymphotrophic virus type III infection of the central nervous system. A preliminary in situ analysis. JAMA 251:2360–2364

    Google Scholar 

  37. Stowring L, Haase AT, Pétursson G, Georgsson G, Pálsson P, Roos R, Szuchet S (1985) Detection of visna virus antigens and RNA in glial cells in foci of demyelination. Virology 141:311–318

    Google Scholar 

  38. Vazeux R, Brousse N, Jarry A, Henin D, Marche C, Vedrenne C, Mikol J, Wolff M, Michon C, Rozenbaum W, Bureau J-F, Montagnier L, Brahic M (1987) AIDS subacute encephalitis: identification of HIV infected cells. Am J Pathol 126:403–410

    Google Scholar 

  39. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MBA (1986) Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 83:7089–7093

    Google Scholar 

  40. Wisniewski HM, Bloom BR (1975) Primary demyelination as a non-specific consequence of a cell-mediated immune reaction. J Exp Med 141:346–359

    Google Scholar 

  41. Yoshikawa T (1968) Atlas of the brains of domestic animals. University of Tokyo Press, Tokyo

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Georgsson, G., Houwers, D.J., Pálsson, P.A. et al. Expression of viral antigens in the central nervous system of visna-infected sheep: an immunohistochemical study on experimentsl visna induced by virus strains of increased neurovirulence. Acta Neuropathol 77, 299–306 (1989). https://doi.org/10.1007/BF00687582

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00687582

Key words

Navigation