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Journal of Virology, January 2006, p. 474-482, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.474-482.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Resistance of Neonatal Mice to Scrapie Is Associated with Inefficient Infection of the Immature Spleen

Michelle Ierna,{dagger} Christine F. Farquhar, George W. Outram, and Moira E. Bruce*

Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, United Kingdom

Received 11 August 2005/ Accepted 7 October 2005

Previous studies demonstrated that neonatal mice up to about a week old are less susceptible than adult mice to infection by intraperitoneal inoculation with mouse-passaged scrapie. In peripherally inoculated adult mice, scrapie replicates in lymphoid tissues such as the spleen before invading the central nervous system. Here, we investigated scrapie susceptibility in neonatal mice in more detail, concentrating on spleen involvement. First, we demonstrated that neonatal mice are about 10 times less susceptible than adults to intraperitoneal scrapie inoculation. Then we injected mice intraperitoneally with a scrapie dose that produced disease in all mice inoculated at 10 days or older but in only about a third of neonatally inoculated mice. In this experiment, spleens collected 70 days after scrapie injection of mice 10 days old or older almost all contained pathological prion protein, PrPSc, and those that were bioassayed all contained high infectivity levels. In contrast, at this early stage, only two of six spleens from neonatally inoculated mice had detectable, low infectivity levels; no PrPSc was detected, even in the two spleens. Therefore, neonatal mice have an impaired ability to replicate scrapie in their spleens, suggesting that replication sites are absent or sparse at birth but mature within 10 days. The increase in susceptibility with age correlated with the first immunocytochemical detection of the normal cellular form of prion protein, PrPc, on maturing follicular dendritic cell networks. As lymphoid tissues are more mature at birth in sheep, cattle, and humans than in mice, our results suggest that in utero infection with scrapie-like agents is theoretically possible in these species.

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

{dagger} Present address: MD Biosciences, Centre for Integrated Diagnostic Systems, University Avenue, Glasgow G12 8QQ, United Kingdom.

Journal of Virology, January 2006, p. 474-482, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.474-482.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Friedman-Levi, Y., Ovadia, H., Hoftberger, R., Einstein, O., Abramsky, O., Budka, H., Gabizon, R. (2007). Fatal Neurological Disease in Scrapie-Infected Mice Induced for Experimental Autoimmune Encephalomyelitis. J. Virol. 81: 9942-9949 [Abstract] [Full Text]  


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