TSE pathogenesis in cattle and sheep

Abstract

-Many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (TSE). Only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (BSE) and scrapie in their natural hosts. In this review, we summarize the most recent insights into the pathogenesis of BSE and scrapie starting from the initial uptake of TSE agents and crossing of the gut epithelium. Following replication in the gut-associated lymphoid tissues (GALT), TSE agents spread to the enteric nervous system (ENS) of the gut. Infection is then carried through the efferent fibers of the post-ganglionic neurons of the parasympathetic and sympathetic nervous system to the pre-ganglionic neurons in the medulla oblongata of the brain and the thoracic segments of the spinal cord. The differences between the pathogenesis of BSE in cattle and scrapie in sheep are discussed as well as the possible existence of additional pathogenetic routes.

Small-Ruminant Lentivirus Enhances PrP Sc Accumulation in Cultured Sheep Microglial Cells

“…Determining the mechanism(s) of the virus-induced enhancement of PrP Sc accumulation warrants further study, which may also help to elucidate some of the basic cellular mechanisms of PrP Sc conversion. During the course of scrapie infection, numerous cell types, including glia, macrophages, and follicular dendritic cells, demonstrate accumulation of PrP Sc (58), but the cell-specific mechanisms that allow for prion conversion are not known. The ability to investigate these mechanisms requires the tools to study PrP Sc infection in these various cell types, mainly having permissive cell culture systems from a variety of cell types.…”

Scientific Opinion on BSE/TSE infectivity in small ruminant tissues

“…Together studies published by (Bellworthy et al, 2005b;van Keulen et al, 2008a) and the data presented by Lantier et al provides an overall picture of the dissemination kinetics of the BSE agent in the organs of orally challenged ARQ/ARQ sheep (see Table 11). Quantitative data on the amount of PrP Sc or infectivity that can be found in tissues from BSE incubating or affected ewes remain extremely limited.…”

Bovine spongiform encephalopathy and food safety

“…The first tissues in which PrP Sc can be detected in BSE are those of the nervous system supplying the intestine 13 although it is not clear how infection reaches the nerves from the intestinal lumen. Infection ascends to the brain via the autonomic nerves 2 .…”

“…Four cases of person-to-person vCJD transmission by blood transfusion have been reported in the UK 13 . Iatrogenic transmission of vCJD remains a concern because retrospective analysis of tonsil and appendix specimens suggests that up to 1 in 4000 persons exposed during the UK epidemic may be a sub-clinical carrier 8,22 .…”