Search

Chronic wasting disease (CWD) is a fatal, transmissible prion disease that affects captive and free-ranging deer, elk, and moose. Although the zoonotic potential of CWD is considered low, identification of multiple CWD strains and the potential for agent evolution upon serial passage hinders a definitive conclusion. Surveillance for CWD in free-ranging populations has documented a continual geographic spread of the disease throughout North America. CWD prions are shed from clinically and preclinically affected hosts, and CWD transmission is mediated at least in part by the environment, perhaps by soil. Much remains unknown, including the sites and mechanisms of prion uptake in the naive host. There are no therapeutics or effective eradication measures for CWD-endemic populations. Continued surveillance and research of CWD and its effects on cervid ecosystems is vital for controlling the long-term consequences of this emerging disease.

Prion diseases are caused by a misfolded isoform of the prion protein, PrPSc. Prion strains are hypothesized to be encoded by strain-specific conformations of PrPSc and prions can interfere with each other when a long-incubation period strain (i.e. blocking strain) inhibits the conversion of a short-incubation period strain (i.e. non-blocking). Prion strain interference influences prion strain dynamics and the emergence of a strain from a mixture; however, it is unknown if two long-incubation period strains can interfere with each other. Here, we show that co-infection of animals with combinations of long-incubation period strains failed to identify evidence of strain interference. To exclude the possibility that this inability of strains to interfere in vivo was due to a failure to infect common populations of neurons we used protein misfolding cyclic amplification strain interference (PMCAsi). Consistent with the animal bioassay studies, PMCAsi indicated that both co-infecting strains were amplifying independently, suggesting that the lack of strain interference is not due to a failure to target the same cells but is an inherent property of the strains involved. Importantly PMCA reactions seeded with long incubation-period strains contained relatively higher levels of remaining PrPC compared to reactions seeded with a short-incubation period strain. Mechanistically, we hypothesize the abundance of PrPC is not limiting in vivo or in vitro resulting in prion strains with relatively low prion conversion efficiency to amplify independently. Overall, this observation changes the paradigm of the interactions of prion strains and has implications for interspecies transmission and emergence of prion strains from a mixture. [ABSTRACT FROM AUTHOR]

Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPSc as the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPSc formation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPSc is more susceptible to degradation when compared to PrPSc from other lymphotrophic strains. We hypothesize that the relative rates of PrPSc formation and clearance can influence prion tropism. [ABSTRACT FROM AUTHOR]

Chronic wasting disease (CWD) is a fatal, transmissible prion disease that affects captive and free-ranging deer, elk, and moose. Although the zoonotic potential of CWD is considered low, identification of multiple CWD strains and the potential for agent evolution upon serial passage hinders a definitive conclusion. Surveillance for CWD in free-ranging populations has documented a continual geographic spread of the disease throughout North America. CWD prions are shed from clinically and preclinically affected hosts, and CWD transmission is mediated at least in part by the environment, perhaps by soil. Much remains unknown, including the sites and mechanisms of prion uptake in the naive host. There are no therapeutics or effective eradication measures for CWD-endemic populations. Continued surveillance and research of CWD and its effects on cervid ecosystems is vital for controlling the long-term consequences of this emerging disease. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on a study which discusses the transmission and adaptation of prions. Topics include the proponents of viral etiology and the protein-only (prion) etiology, prion tropism, and prion strains. Also mentioned are the prion diseases of animals, patterns of pathology in Parkinson's disease, and implications of findings of prion disease research for human health.