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Journal of Virology, January 2000, p. 828-833, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Entry versus Blockade of Brain Infection following Oral or Intraperitoneal Scrapie Administration: Role of Prion Protein Expression in Peripheral Nerves and Spleendagger

Richard Race,1 Michael Oldstone,2 and Bruce Chesebro1,*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana 59840,1 and Division of Virology, Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 920372

Received 18 June 1999/Accepted 11 October 1999

Naturally occurring transmissible spongiform encephalopathy (TSE) diseases such as bovine spongiform encephalopathy in cattle are probably transmitted by oral or other peripheral routes of infection. While prion protein (PrP) is required for susceptibility, the mechanism of spread of infection to the brain is not clear. Two prominent possibilities include hematogenous spread by leukocytes and neural spread by axonal transport. In the present experiments, following oral or intraperitoneal infection of transgenic mice with hamster scrapie strain 263K, hamster PrP expression in peripheral nerves was sufficient for successful infection of the brain, and cells of the spleen were not required either as a site of amplification or as transporters of infectivity. The role of tissue-specific PrP expression of foreign PrP in interference with scrapie infection was also studied in these transgenic mice. Peripheral expression of heterologous PrP completely protected the majority of mice from clinical disease after oral or intraperitoneal scrapie infection. Such extensive protection has not been seen in earlier studies on interference, and these results suggested that gene therapy with mutant PrP may be effective in preventing TSE diseases.

* Corresponding author. Mailing address: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840-2999. Phone: (406) 363-9354. Fax: (406) 363-9286. E-mail: bchesebro{at}nih.gov.

dagger Publication 11526-NP from the Division of Virology, Department of Neuropharmacology, Scripps Research Institute.

Journal of Virology, January 2000, p. 828-833, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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