Prion strains: shining new light on old concepts

Block, Alyssa J; Bartz, Jason C.

doi:10.1007/s00441-022-03665-2

Cited by 20 publications

(14 citation statements)

References 183 publications

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“…This chapter addresses new insights into structural aspects of PrP Sc and how this knowledge helps to advance our molecular understanding of how species barriers and prion strains are determined. Jason Bartz starts out by describing the history of prions strains, how concepts evolved, and how in fact prion strains evolve, mutate, and adapt to new species (Block and Bartz 2022). The next chapter, by Debbie McKenzie and colleagues focusses on the emergence of CWD strains, summarizing the characteristics of known CWD strains and describing the impact of PrP polymorphisms on the generation of new strains (Otero et al 2022).…”

Section: Evolving Concepts On Strains Species Barrier and Structurementioning

confidence: 99%

New developments in prion disease research

Gilch

Schätzl

2023

Cell Tissue Res

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Prion diseases are fatal and infectious neurodegenerative disorders and prototypic conformational diseases. They are caused by the structural conversion of the cellular prion protein (PrP C ) into the pathological PrP Sc isoform. Examples are scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and Creutzfeldt-Jacob disease (CJD) in humans. The concept that a protein can constitute an infectious agent is now widely accepted. Even more, prion-like features of proteins playing central roles in the pathogenesis of other neurodegenerative diseases were described in recent years. Prions are transmissible within and sometimes between species. This was highlighted by the BSE epidemic that devastated entire economies and resulted in infections of humans and several other species. Whereas BSE was widely contained by an international package of complementary measures, another animal prion disease is currently taking center stage: CWD. Prion research traditionally uses a highly multi-disciplinary approach, from structural biology to field research. This special issue highlights recent developments and discusses progress and remaining challenges. Leading researchers describe new concepts, experimental models, and technologies that drive prion research. Reviews grouped in chapters describe recent advances in the understanding of the infectious unit and the molecular determinants of prion strains and new findings in the cell biology of prions. Experts discuss the modern diagnosis of prion diseases and its influence on the diagnosis of other neurodegenerative disorders. Finally, therapeutic targets and strategies for therapy and prophylaxis are described, although a final cure for these devastating diseases is not yet at the horizon.

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Section: Evolving Concepts On Strains Species Barrier and Structurementioning

confidence: 99%

New developments in prion disease research

Gilch

Schätzl

2023

Cell Tissue Res

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“…As a result, strain differences can influence important disease characteristics including interspecies transmission, ability to detect prion infections, and potential for the disease agent to survive inactivation and/or persist in the environment. The structure of the disease-associated form of the prion protein (PrP Sc ) is undoubtedly the basis of prion strain differences and has been shown to differ between prion strains (reviewed in Block and Bartz 2022). Although not required for strain generation, the prion protein primary structure (i.e., amino acid sequence) can play an important role in strain generation and selection (Duque Velasquez et al 2020;Hannaoui et al 2017).…”

Section: Prp Structure and Prion Strainsmentioning

confidence: 99%

Emergence of CWD strains

et al. 2022

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Chronic wasting disease (CWD) strains present a novel challenge to defining and mitigating this contagious prion disease of deer, elk, moose, and reindeer. Similar to strains of other prion diseases (bovine spongiform encephalopathy, sheep scrapie), CWD strains can affect biochemical and neuropathological properties of the infectious agent, and importantly interspecies transmission. To date, ten CWD strains have been characterized. The expanding range of CWD in North America and its presence in South Korea as well as Scandinavian countries will potentially result in millions of cervids infected with CWD; thus, novel strains will continue to emerge. In this review, we will summarize the characteristics of known CWD strains and describe the impact of prion protein gene polymorphisms on the generation of strains. We will also discuss the evidence that individual cervids can harbor more than one CWD strain, complicating strain analysis, and affecting selection and adaptation of strains in new hosts.

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“…Strain adaptations often occur when prions are passaged through new hosts [ 16 ] where cellular differences such as cofactor availability [ 17 ] result in phenotypic change such as altered incubation time and PrP D deposition [ 18 ]. For example, sheep scrapie passed through either mice or goats, and then mice, has given rise to multiple strains of rodent adapted scrapie, each with distinct clinical and biochemical manifestations [ 19 ]. The gold standard for investigating prion strain phenomenon remains mouse bioassay [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Sporadic Creutzfeldt–Jakob disease infected human cerebral organoids retain the original human brain subtype features following transmission to humanized transgenic mice

Groveman

Race

Foliaki

et al. 2023

acta neuropathol commun

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Human cerebral organoids (COs) are three-dimensional self-organizing cultures of cerebral brain tissue differentiated from induced pluripotent stem cells. We have recently shown that COs are susceptible to infection with different subtypes of Creutzfeldt–Jakob disease (CJD) prions, which in humans cause different manifestations of the disease. The ability to study live human brain tissue infected with different CJD subtypes opens a wide array of possibilities from differentiating mechanisms of cell death and identifying neuronal selective vulnerabilities to testing therapeutics. However, the question remained as to whether the prions generated in the CO model truly represent those in the infecting inoculum. Mouse models expressing human prion protein are commonly used to characterize human prion disease as they reproduce many of the molecular and clinical phenotypes associated with CJD subtypes. We therefore inoculated these mice with COs that had been infected with two CJD subtypes (MV1 and MV2) to see if the original subtype characteristics (referred to as strains once transmitted into a model organism) of the infecting prions were maintained in the COs when compared with the original human brain inocula. We found that disease characteristics caused by the molecular subtype of the disease associated prion protein were similar in mice inoculated with either CO derived material or human brain material, demonstrating that the disease associated prions generated in COs shared strain characteristics with those in humans. As the first and only in vitro model of human neurodegenerative disease that can faithfully reproduce different subtypes of prion disease, these findings support the use of the CO model for investigating human prion diseases and their subtypes.

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Prion strains: shining new light on old concepts

Cited by 20 publications

References 183 publications

New developments in prion disease research

New developments in prion disease research

Emergence of CWD strains

Sporadic Creutzfeldt–Jakob disease infected human cerebral organoids retain the original human brain subtype features following transmission to humanized transgenic mice

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