Foodborne-Transmitted Prions From the Brain of Cows With Bovine Spongiform Encephalopathy Ascend in Afferent Neurons to the Simian Central Nervous System and Spread to Tonsils and Spleen at a Late Stage of the Incubation Period.

Abstract

BACKGROUND:

Protease-resistant prion protein (PrP(res)) accumulation in lymphoreticular tissues indicates prion infection. To date, tonsillectomy and appendectomy samples have been used in population prevalence surveys to detect clinically silent carriers of variant Creutzfeldt-Jakob disease (vCJD). However, the temporal sequence of prion spread in the human body is still not known. We therefore traced the temporal-spatial pattern of PrP(res) accumulation in the body of a simian vCJD model.

METHODS:

Cynomolgus monkeys were fed brain of (eleven) cows with bovine spongiform encephalopathy, and some were euthanized before and some after onset of neurological signs. PrP(res) was detected in tissues by a paraffin-embedded tissue blot technique and a semiquantitative Western immunoblot assay.

RESULTS:

Bovine spongiform encephalopathy (BSE)-associated prions were preferentially transported from the gut to the central nervous system (CNS) along sensory nerve fibers and initially entered the simian CNS at lumbar spinal cord levels. In asymptomatic animals, we found BSE in 50% and 12% of gut- and tonsil-derived samples, respectively.

CONCLUSIONS:

Unlike in rodents and ruminants, foodborne BSE-associated prions entered the simian CNS via afferent neurons. From sites of initial CNS invasion, prions spread centrifugally to tonsils and spleen at an advanced stage of the incubation period, thus explaining why tonsil specimens were not reliable for detection of simian disease carriers before onset of clinical signs.

• Authors: Edgar Holznagel, Barbara Yutzy, Carina Kruip, Par Bierke, Walter Schulz-Schaeffer, Johannes Löwer
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 212 Issue 9 Pg. 1459-68 (Nov 01 2015) ISSN: 1537-6613 [Electronic] United States
• PMID: 25895987 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• PrPSc Proteins

Topics

• Animals
• Brain (pathology)
• Cattle
• Central Nervous System (pathology)
• Creutzfeldt-Jakob Syndrome (epidemiology, veterinary)
• Disease Models, Animal
• Encephalopathy, Bovine Spongiform (transmission)
• Foodborne Diseases (pathology, veterinary)
• Macaca fascicularis
• Meat Products
• Neurons, Afferent (pathology)
• Palatine Tonsil (pathology)
• PrPSc Proteins (metabolism)
• Prevalence
• Specimen Handling
• Spleen (pathology)