| Subviral Agents: | Prions |
| Nucleic Acid: | None |
| General Host: | Vertebrates Fungi |
| Agent | 90.001. Prions |
Taxonomic Structure of Prions
Type 90.001. Mammalian PrionsPrion 90.001.0.01. Agents of Spongiform Encephalopathies
Type 90.002. Fungal Prions
Prion 90.002.0.01. [URE2] prion
Prion 90.002.0.02. [PSI] prion
Prion 90.002.0.03. [Het-s] prion
| Type | 90.001. Mammalian Prions |
Definition
Prions are small, proteinaceous infectious particles that resist inactivation by procedures which affect nucleic acids. To date, no detectable nucleic acids of any kind and no virus-like particles have been associated with prions. Prions cause scrapie and other spongiform encephalopathies of animals and humans.
| Prion | 90.001.0.01. Agents of Spongiform Encephalopathies |
List of Prion Species
| Virus Code | Disease abbreviation | Natural host | Prion | PrP isoform | |
| 90.001.0.01.001. | Scrapie | sheep & goats | Scrapie prion | OvPrPSc | |
| 90.001.0.01.002. | Transmissible mink encephalopathy (TME) | mink | TME prion | MkPrPSc | |
| 90.001.0.01.003. | Chronic wasting disease (CWD) | mule deer & elk | CWD prion | MDePrPSc | |
| 90.001.0.01.004. | Bovine spongiform encephalopathy (BSE) | cattle | BSE prion | BovPrPSc | |
| 90.001.0.01.005. | Feline spongiform encephalopathy (FSE) | cats | FSE prion | FePrPSc | |
| 90.001.0.01.006. | Exotic ungulate encephalopathy (EUE) | nyala & greater kudu | EUE prion | NyaPrPSc | |
| 90.001.0.01.007. | Kuru | humans | Kuru prion | HuPrPSc | |
| 90.001.0.01.008. | Creutzfeldt-Jakob disease (CJD) | humans | CJD prion | HuPrPSc | |
| 90.001.0.01.009. | Gerstmann-Sträussler-Scheinker syndrome (GSS) | humans | GSS prion | HuPrPSc | |
| 90.001.0.01.010. | Fatal familial insomnia (FFI) | humans | FFI prion | HuPrPSc |
Prions are composed largely, if not entirely, of a protein designated as the scrapie isoform of the prion protein, PrPSc (see Table 2 for glossary). A post-translational process, as yet undefined, generates PrPSc from the normal cellular isoform of the protein, designated PrPC. Both PrPSc and PrPC are encoded by a single copy chromosomal gene. Although the inoculated prion initiates the production of PrPSc, its synthesis originates from the host PrP gene.
Several features distinguish prions from viruses. First, prions can exist in multiple molecular forms, whereas viruses exist in a single form with distinct ultrastructural morphology. Second, prions are non-immunogenic, in contrast to viruses, which almost always provoke an immune response. Third, there is no evidence for an essential nucleic acid within the infectious prion particle, whereas viruses have a nucleic acid genome which serves as the template for the synthesis of progeny virus. Fourth, the only known component of the prion is PrPSc, which is encoded by a chromosomal gene, whereas viruses are composed of nucleic acid, proteins, and often other constituents.
Several features distinguish prions from viruses. First, prions can exist in multiple molecular forms, whereas viruses exist in a single form with distinct ultrastructural morphology. Second, prions are non-immunogenic, in contrast to viruses, which almost always provoke an immune response. Third, there is no evidence for an essential nucleic acid within the infectious prion particle, whereas viruses have a nucleic acid genome which serves as the template for the synthesis of progeny virus. Fourth, the only known component of the prion is PrPSc, which is encoded by a chromosomal gene, whereas viruses are composed of nucleic acid, proteins, and often other constituents.
Nomenclature
Although the prions that cause TME and BSE are referred to as TME prions and BSE prions, this may be unjustified, because both are thought to originate from the oral consumption of scrapie prions in sheep-derived foodstuffs and because many lines of evidence argue that the only difference among the various prions is the sequence of PrP which is dictated by the host and not the prion itself.
The human prions present a similar semantic conundrum. Transmission of human prions to laboratory animals produces prions carrying PrP molecules with sequences dictated by the PrP gene of the host, not that of the inoculum. To simplify the terminology, it has been suggested that the disease-related PrP isoform be designated PrPSc without regard to the origin of the prion (Table 1). Alternatively, the superscript of the disease-related PrP isoform can be used to signify the host in which the prion disease originated. For added specificity, a variant or mutant PrP can be noted in parentheses (Table 3) [e.g., the prion found in the I/Ln mouse which has a PrP variant with F at codon 108 And V at 189 can be identified as MoPrP(108F, 189V)Sc; similarly, the prion found in a Libyan Jewish CJD patient homozygous for the mutation K at codon 200 can be identified as HuPrP(200K)Sc]. For heterozygous situations, and where the allele that determines the PrP form is not known, HuPrPSc, or HuPrPCJD, can be used as a default.
Distinguishing among CJD, GSS and FFI has grown increasingly difficult with the recognition that familial CJD, GSS and FFI are autosomal dominant diseases that are caused by mutations in the PRNP gene. Initially, it was thought that a specific PrP mutation was associated with a particular clinical / neuropathological presentation. Now, an increasing number of exceptions are being recognized. In a single family with a particular PrP mutation, different clinical / neuropathologic manifestations can be seen. It has been suggested that the disorders be labeled "inherited prion disease," followed by an identification of the mutation. For example, most patients with a PrP mutation at codon 102 present with ataxia and have PrP amyloid plaques; these patients are generally diagnosed as GSS, but some individuals within these families present with dementia characteristic of CJD.
The human prions present a similar semantic conundrum. Transmission of human prions to laboratory animals produces prions carrying PrP molecules with sequences dictated by the PrP gene of the host, not that of the inoculum. To simplify the terminology, it has been suggested that the disease-related PrP isoform be designated PrPSc without regard to the origin of the prion (Table 1). Alternatively, the superscript of the disease-related PrP isoform can be used to signify the host in which the prion disease originated. For added specificity, a variant or mutant PrP can be noted in parentheses (Table 3) [e.g., the prion found in the I/Ln mouse which has a PrP variant with F at codon 108 And V at 189 can be identified as MoPrP(108F, 189V)Sc; similarly, the prion found in a Libyan Jewish CJD patient homozygous for the mutation K at codon 200 can be identified as HuPrP(200K)Sc]. For heterozygous situations, and where the allele that determines the PrP form is not known, HuPrPSc, or HuPrPCJD, can be used as a default.
Distinguishing among CJD, GSS and FFI has grown increasingly difficult with the recognition that familial CJD, GSS and FFI are autosomal dominant diseases that are caused by mutations in the PRNP gene. Initially, it was thought that a specific PrP mutation was associated with a particular clinical / neuropathological presentation. Now, an increasing number of exceptions are being recognized. In a single family with a particular PrP mutation, different clinical / neuropathologic manifestations can be seen. It has been suggested that the disorders be labeled "inherited prion disease," followed by an identification of the mutation. For example, most patients with a PrP mutation at codon 102 present with ataxia and have PrP amyloid plaques; these patients are generally diagnosed as GSS, but some individuals within these families present with dementia characteristic of CJD.
| Type | 90.002. Fungal Prions |
List of Fungal Prions
Derivation of Name
Prion: singla for proteinaceous and infectious particle
[URE3] and URE2 from "ureidosuccinate"
[Het-s] and het-s from "heteronkaryon" incompatibility
[PSI] from the greek letter Psi
[URE3] and URE2 from "ureidosuccinate"
[Het-s] and het-s from "heteronkaryon" incompatibility
[PSI] from the greek letter Psi
Contributed by
Prusiner SB, Baldwin M, Collinge J, DeArmond SJ, Marsh R, Tateishi J, Weissmann C
Last Updated 14-Feb-02
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