1887

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Volume 77, Issue 7

Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy Free

Abstract

The development of transmissible spongiform encephalopathies in experimental models depends on two major factors: the intracerebral accumulation of an abnormal, protease-resistant isoform of PrP (PrP), which is a host protein mainly expressed in neurons; and the existence of different strains of agent. In order to make a distinction between pathogenic mechanisms depending upon the accumulation of host-derived PrP and the strain-specific effects, we quantified and compared the sequence of molecular [PrP and glial fibrillary acidic protein (GFAP) accumulation] and pathological events in the brains of syngeneic mice throughout the course of infection with two different strains of agent. The bovine spongiform encephalopathy (BSE) agent exhibits properties different from any known scrapie source and has been studied in comparison with a classical scrapie strain. Convergent kinetic data in both models confirmed the cause-effect relationship between PrP and pathological changes and showed that PrP accumulation is directly responsible for astrocyte activation . Moreover, we observed a threshold level of PrP for this effect on astroglial cells. However, despite similar infectivity titres, the BSE model produced less PrP than scrapie, and the relative importance of gliosis was higher. The comparison of the molecular and pathological features after intracerebral or intraperitoneal inoculation also revealed differences between the models. Therefore, the mechanisms leading to the targeting and the fine regulation of the molecular events seem to be independent of the host PrP and to depend upon the agent. The possible involvement of a regulatory molecule accounting for these specificities has to be considered.

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  • Accepted:
  • Published Online:
© Journal of General Virology 1996
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1996-07-01
2024-04-16
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Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy
J. Gen. Virol. 77, 1601 (1996); https://doi.org/10.1099/0022-1317-77-7-1601
/content/journal/jgv/10.1099/0022-1317-77-7-1601
/content/journal/jgv/10.1099/0022-1317-77-7-1601
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