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Isolation and growth of a cytopathic agent from multiple sclerosis brain tissue

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Abstract

Although many studies support a role for viruses in multiple sclerosis (MS) etiopathology, no specific agent has been consistently associated with significant numbers of MS patients without concomitant detection in non-MS controls. Previous studies have shown the presence of viral-like structures in MS plaques, although the specificity of these structures for MS has been questioned. The present study describes the use of polyclonal antisera against feline and human brain-derived cytopathic agents and immunoaffinity chromatography to purify and partially characterize possible virus-like structures from MS brain tissue. Chromatography eluates from 4 MS brains contained pleomorphic particles up to 350 nm in diameter and tubular/filamentous-like structures approximately 10–18 nm in thickness. Inoculation of primary rat glial cell cultures with chromatography eluates from MS brain tissue resulted in a reproducible pattern of cytopathic effects in the form of multinucleation in cells identified immunocytochemically as oligodendrocytes. Antisera raised against the feline and MS-derived cytopathic agents were used to successfully immunolabel infected oligodendrocyte-like cells and syncytia and to detect a 66,000 Mr protein on Western blots of inoculated cultures or concentrated MS brain eluates. Similar structures, cytopathic effects (CPE) and protein expression were not observed in eluates from 5 control brains or in cultures inoculated with control brain eluates. These studies demonstrate that cytopathic, virus-like structures can be isolated from MS brain tissue using antisera raised against a cytopathic agent rescued from demyelinating brain lesions in cats. The identity of this agent and its possible role in MS aetio-pathology remains unknown.

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Authors and Affiliations

  1. Veterinary and Biomedical Sciences, Murdoch University, Murdoch, Western Australia

    Anthony R. White, Nichole S. Dutton & Robert D. Cook

  2. CNS Infection and Immunity Group, Department of Neurogenetics, Imperial College School of Medicine (St Mary’s campus), Norfolk Place, W2 1PG, London, England

    Anthony R. White

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  1. Anthony R. White
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  2. Nichole S. Dutton
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  3. Robert D. Cook
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Correspondence to Anthony R. White.

Additional information

The constructive editorial comments of Dr G Wilcox and the expert technical assistance of Dr D Berryman and Mr P Fallon are greatly appreciated as is the donation of the anti-CNPase antisera by Dr TJ Sprinkle. Mr G Griffiths and Mr B Kreunen assisted in the preparation of the micrographs. The research was supported by a grant from the School of Veterinary Studies, Murdoch University. ARW was a recipient of an Australian Postgraduate Research Award.

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White, A.R., Dutton, N.S. & Cook, R.D. Isolation and growth of a cytopathic agent from multiple sclerosis brain tissue. Journal of NeuroVirology 8, 111–121 (2002). https://doi.org/10.1080/13550280290049543

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  • DOI: https://doi.org/10.1080/13550280290049543

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