Abstract
Transmissible spongiform encephalopathies or prion disorders are fatal infectious diseases that cause characteristic spongiform degeneration in the central nervous system. The causative agent, the so-called prion, is an unconventional infectious agent that propagates by converting the host-encoded cellular prion protein PrP into ordered protein aggregates with infectious properties. Prions are devoid of coding nucleic acid and thus rely on the host cell machinery for propagation. While it is now established that, in addition to PrP, other cellular factors or processes determine the susceptibility of cell lines to prion infection, exact factors and cellular processes remain broadly obscure. Still, cellular models have uncovered important aspects of prion propagation and revealed intercellular dissemination strategies shared with other intracellular pathogens. Here, we summarize what we learned about the processes of prion invasion, intracellular replication and subsequent dissemination from ex vivo cell models.
Highlights
Transmissible spongiform encephalopathies or prion diseases are neurodegenerative diseases that are characterized by the deposition of host-encoded prion proteins as highly stable, beta-sheet rich polymeric aggregates in the central nervous system [1]
Experiments with 22Linfected primary astrocytes demonstrated that efficient intercellular transfer of PrPSc to recipient CAD cells was predominately due to close cell contact, suggesting that tunneling nanotubes or other cellular contacts facilitate prion transfer [96]
Concerted efforts in the last couple of years have provided us with long-awaited cellular models for propagation of bovine and human prions
Summary
Transmissible spongiform encephalopathies or prion diseases are neurodegenerative diseases that are characterized by the deposition of host-encoded prion proteins as highly stable, beta-sheet rich polymeric aggregates in the central nervous system [1]. Prion diseases are mainly sporadic, with some genetic cases. Both iatrogenic and zoonotic transmissions have been reported [1]. When introduced into the same mammalian species, prions can cause disease phenotypes that differ in incubation times, clinical presentation, host organ and cell tropism and neuropathological characteristics such as PrPSc deposition patterns and spongiform degeneration [7]. Prions are cell-associated pathogens that transmit to neighboring cells by different routes These include the potential release of naked PrPSc molecules [13], transfer to neighboring cells by direct cell contact [14,15] or secretion of PrPSc in association with extracellular vesicles by infected cells [16]. How exactly is PrPSc taken up by recipient cells and how do PrP-derived prion strains differ in their cellular propagation and dissemination routes? PrP-derived prions enter and replicate within their target cells
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