How do PrPSc Prions Spread between Host Species, and within Hosts?

Abstract

Prion diseases are sub-acute neurodegenerative diseases that affect humans and some domestic and free-ranging animals. Infectious prion agents are considered to comprise solely of abnormally folded isoforms of the cellular prion protein known as PrP^Sc. Pathology during prion disease is restricted to the central nervous system where it causes extensive neurodegeneration and ultimately leads to the death of the host. The first half of this review provides a thorough account of our understanding of the various ways in which PrP^Sc prions may spread between individuals within a population, both horizontally and vertically. Many natural prion diseases are acquired peripherally, such as by oral exposure, lesions to skin or mucous membranes, and possibly also via the nasal cavity. Following peripheral exposure, some prions accumulate to high levels within the secondary lymphoid organs as they make their journey from the site of infection to the brain, a process termed neuroinvasion. The replication of PrP^Sc prions within secondary lymphoid organs is important for their efficient spread to the brain. The second half of this review describes the key tissues, cells and molecules which are involved in the propagation of PrP^Sc prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. This section also considers how additional factors such as inflammation and aging might influence prion disease susceptibility.

Keywords: PrPSc; central nervous system; horizontal transmission; intestine; prion protein; prions; secondary lymphoid organs; vertical transmission.

Figure 1

Cartoon summarizing the potential routes of prion exposure in animals such as sheep, and mechanisms in which prions may be disseminated between animals. Red arrows, routes of prion exposure; Broken blue arrows, routes of prion shedding or secretion from an infected animal.

Figure 2

The cells involved in the spread of prions from the intestine to the central nervous system (CNS). After oral exposure the replication of prions upon follicular dendritic cells (FDC) in the Peyer’s patches in the intestine is essential to establish host infection. With the Peyer’s patches, the prions exploit an elegant cellular relay to make their way from the lumen of intestine to the nervous system.