Subclinical prion disease induced by oral inoculation.
Natural transmission of prion disease is believed to occur by peripheral infection such as oral inoculation. Following this route of inoculation, both the peripheral nervous system and the lymphoreticular system may be involved in the subsequent neuroinvasion of the central nervous system by prions, which may not necessarily result in clinical signs of terminal disease. Subclinical prion disease, characterized by the presence of infectivity and PrP(Sc) in the absence of overt clinical signs, may occur. It is not known which host factors contribute to whether infection with prions culminates in a terminal or subclinical disease state. We have investigated whether the level of host PrP(c) protein expression is a factor in the development of subclinical prion disease. When RML prion inoculum was inoculated by either the i.c. or intraperitoneal route, wild-type and tga20 mice both succumbed to terminal prion disease. In contrast, orally inoculated tga20 mice succumbed to terminal prion disease, whereas wild-type mice showed no clinical signs. However, wild-type mice sacrificed 375 or 525 days after oral inoculation harbored significant levels of brain PrP(Sc) and infectivity. These data show that same-species transmission of prions by the oral route in animals that express normal levels of PrP(c) can result in subclinical prion disease. This indicates that the level of host PrP(c) protein expression is a contributing factor to the regulation of development of terminal prion disease. Events that increase PrP(c) expression may predispose a prion-infected animal to the more deleterious effects of prion pathology.
Thackray
Alana M
AM
Department of Clinical Veterinary Medicine, Centre for Veterinary Science, University of Cambridge, Madingley Road, Cambridge, United Kingdom CB3 OES.
Klein
Michael A
MA
Bujdoso
Raymond
R
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000473:pathology / Q000503:physiopathology*; D011328:Prions / Q000008:administration & dosage* / Q000472:pathogenicity*; D013154:Spleen / Q000378:metabolism / Q000473:pathology
D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions