The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies

Abstract

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that are caused by unconventional pathogens and affect the central nervous system of animals and humans. Several different forms of these diseases result from natural infection (i.e. exposure to transmissible spongiform encephalopathy agents or prions, present in the natural environment of the respective host). This holds true also for scrapie in sheep, bovine spongiform encephalopathy in cattle, chronic wasting disease in elk and deer, or variant Creutzfeldt–Jakob disease in humans, all of which are assumed to originate predominantly from peroral prion infection. This article intends to provide an overview of the current state of knowledge on the spread of scrapie, chronic wasting disease, bovine spongiform encephalopathy and variant Creutzfeldt–Jakob disease agents through the body in naturally affected hosts, and in model animals experimentally challenged via the alimentary tract. Special attention is given to the tissue components and spreading pathways involved in the key stages of prion routing through the body, such as intestinal uptake, neuroinvasion of nerves and the central nervous system, and centrifugal spread from the brain and spinal cord to peripheral sites (e.g. sensory ganglia or muscles). The elucidation of the pathways and mechanisms by which prions invade a host and spread through the organism can contribute to efficient infection control strategies and the improvement of transmissible spongiform encephalopathy diagnostics. It may also help to identify prophylactic or therapeutic approaches that would impede naturally acquired transmissible spongiform encephalopathy infections.

PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice infected orally with bovine spongiform encephalopathy

“…The late centrifugal spread of PrP TSE from the CNS to muscle in orally BSE-infected mice is also consistent with observations in other experimental models (Thomzig et al, 2004;Herzog et al, 2005) or in scrapie-infected sheep (Andréoletti et al, 2004), where the CNS plays a primary role in the dissemination of infectivity to muscles (Beekes & McBride, 2007).…”

“…The presence and distribution of infectivity or PrP TSE accumulation in muscles of 'natural' TSE infections differ in different host-strain combinations (Andréoletti et al, 2004;Angers et al, 2006;Beekes & McBride, 2007;Bosque et al, 2002;Casalone et al, 2005;Glatzel et al, 2003;Herzog et al, 2005;Peden et al, 2006;Thomzig et al, 2004Thomzig et al, , 2006. This heterogeneity has also been observed in experimental models of TSEs.…”

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

“…SD: 10,641.04 (free medium) and 10,786.49 (PrP Sc -loaded medium). The experiment was repeated four times (Luhr et al 2002(Luhr et al , 2004 our model used peripheral primary neurons that were infected in vivo after oral scrapie challenge (Beekes and McBride 2007). Thus our model speciWcally targeted a cell-to-cell transmission of PrP Sc (Caughey and Baron 2006) from the immune system to the PNS, hypothetically at the genesis of the prion peripheral neuroinvasion (Kimberlin and Walker 1989).…”

Pathogenesis of Chronic Wasting Disease in Cervidized Transgenic Mice

“…Such a pattern is typical of the progressive vagal and sympathetic nervous system-mediated, centrifugal dissemination of prions from the brain in the later to terminal stages of prion disease as described in previous mouse, sheep, and hamster models. 24,[53][54][55][56] In the successfully infected Tg[CerPrP] mice, there were exceptions to the proposed two-to three-step pathogenesis, ie, instances in which PrP RES was identified in peripheral tissues either before or simultaneous with its identification in the CNS. Such cases included the identification of PrP RES in the spleen or liver of i.v., i.p., and i.c.…”