NR ATYD
AU Ierna,M.; Farquhar,C.F.; Outram,G.W.; Bruce,M.E.
TI Resistance of neonatal mice to scrapie is associated with inefficient infection of the immature spleen
QU Journal of Virology 2006 Jan; 80(1): 474-82
PT journal article; research support, non-u.s. gov't
AB 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.
IN Gegenüber intraperitonealer Inokulation mit Hausmaus-adaptiertem Scrapie sind neugeborene Hausmäuse um eine Größenordnung weniger empfänglich als erwachsene Hausmäuse. Während bei im Alter von mindestens 10 Tagen intraperitoneal inokulierten Hausmäusen nach 90 Tagen eine hohe Infektiosität und PrPsc in der Milz nachweisbar sind, fanden die Autoren in der Milz nur manchmal eine geringe Infektiosität und kein PrPsc. Es scheint so, als fehlten neugeborenen Hausmäusen in der Milz noch die Zellen, die PrPsc vermehren können.
MH Animals; Animals, Newborn; Dendritic Cells, Follicular/*drug effects; Infusions, Parenteral; Mice; Mice, Inbred C57BL; Mice, Knockout; PrPsc Proteins/administration & dosage/metabolism/*pathogenicity; Scrapie/*genetics; Spleen/physiology/*virology
AD Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, United Kingdom. moira.bruce@bbsrc.ac.uk.
SP englisch
PO USA