Prion biology relevant to bovine spongiform encephalopathy1

Abstract

Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE literature is characterized by subsequently unsupported claims of species barriers or absolute tissue safety. This review presents an overview of TSE and summarizes recent research on pathogenesis and transmission.

Influence of the geographic distribution of prion protein gene sequence variation on patterns of chronic wasting disease spread in white-tailed deer (Odocoileus virginianus)

“…Given the resilience of the infectious prion [23], the relative ease of transmission [24], and the uncertain interspecific barrier to transmission [25–27], a response plan is necessary as more is learned about the health and economic impacts of CWD. Therefore, management has primarily focused on containment utilizing various combinations of expanded surveillance, restrictions on movement or translocation of susceptible individuals, public hunting, and culling by government agencies [4,28–31].…”

Nutritive value of ensiled pig excreta, poultry litter or urea with molasses or bakery by-products in diets for lambs

“…Experimental transmission of bovine spongiform encephalopathy to sheep has been demonstrated, but the low prion level in non-nervous tissues (i.e. gut) in litter and the low probability of cross-species infection represent minimal risk of animal excreta as source of transmissible prion disease (Novakofski et al, 2005). Therefore, the objective of this study was to evaluate in lambs the nutritional value of total mixed rations with maize stover silage fortified with pig excreta, poultry litter or urea as N sources, and with molasses or bakery by-products as energy sources.…”

The identification of candidate genes and SNP markers for classical bovine spongiform encephalopathy susceptibility

“…11,12 This resistance results in the accumulation of the non-degraded form of the protein which results in the neural degeneration and spongiform appearance of infected CNS tissues. 4 In classical BSE, the pathogenesis of the disease is the result of the transference of the infectious prion from the digestive tract into the peripheral nervous system and then to the brain. 5 Studies of the pathogenesis have concluded that the route of transmission is from the ileal Peyer's patches and the tonsils through the parasympathetic and sympathetic nerve fibers of the autonomous nervous system.…”

“…3 TSEs are unique in that they may be genetic, sporadic or transmitted but, in all cases the disease state is associated with accumulation of the abnormal PrP Res in the brain and central nervous system (CNS) causing degeneration. 4 Classical BSE is a form of TSE acquired by the consumption of meat and/or bone meal contaminated with the (PrP Res ) or infectious prion agent 5 and was first observed in the United Kingdom (UK) in 1986. 6 A large number of infected animals entered the food chain in the preclinical state and were consumed by the human population in the UK and elsewhere.…”