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Journal of Virology, October 2001, p. 9320-9327, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9320-9327.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Early Spread of Scrapie from the Gastrointestinal Tract to the Central Nervous System Involves Autonomic Fibers of the Splanchnic and Vagus Nerves

Patricia A. McBride,1,* Walter J. Schulz-Schaeffer,2,dagger Maura Donaldson,1 Moira Bruce,1 H. Diringer,3 Hans A. Kretzschmar,2 and Michael Beekes3

Neuropathogenesis Unit, Institute for Animal Health, Edinburgh EH9 3JF, United Kingdom,1 and Institut für Neuropathologie, 81377 Munich,2 and Robert Koch-Institut, 13353 Berlin,3 Germany

Received 19 March 2001/Accepted 11 June 2001

Although the ultimate target of infection is the central nervous system (CNS), there is evidence that the enteric nervous system (ENS) and the peripheral nervous system (PNS) are involved in the pathogenesis of orally communicated transmissible spongiform encephalopathies. In several peripherally challenged rodent models of scrapie, spread of infectious agent to the brain and spinal cord shows a pattern consistent with propagation along nerves supplying the viscera. We used immunocytochemistry (ICC) and paraffin-embedded tissue (PET) blotting to identify the location and temporal sequence of pathological accumulation of a host protein, PrP, in the CNS, PNS, and ENS of hamsters orally infected with the 263K scrapie strain. Enteric ganglia and components of splanchnic and vagus nerve circuitry were examined along with the brain and spinal cord. Bioassays were carried out with selected PNS constituents. Deposition of pathological PrP detected by ICC was consistent with immunostaining of a partially protease-resistant form of PrP (PrPSc) in PET blots. PrPSc could be observed from approximately one-third of the way through the incubation period in enteric ganglia and autonomic ganglia of splanchnic or vagus circuitry prior to sensory ganglia. PrPSc accumulated, in a defined temporal sequence, in sites that accurately reflected known autonomic and sensory relays. Scrapie agent infectivity was present in the PNS at low or moderate levels. The data suggest that, in this scrapie model, the infectious agent primarily uses synaptically linked autonomic ganglia and efferent fibers of the vagus and splanchnic nerves to invade initial target sites in the brain and spinal cord.

* Corresponding author. Mailing address: Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Rd., Edinburgh EH9 3JF, United Kingdom. Phone: 44(0)131 667 5204. Fax: 44(0)131 668 3872. E-mail: tricia.mcbride{at}bbsrc.ac.uk.

dagger Present address: Institute für Neuropathologie, 37075 Göttingen, Germany.

Journal of Virology, October 2001, p. 9320-9327, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9320-9327.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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