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Human transmissible spongiform encephalopathies: historic view.
Handb Clin Neurol. 2018; 153:1-17.HC

Abstract

The first of several pivotal moments leading to current understanding of human transmissible spongiform encephalopathies (TSEs) occurred in 1959 when veterinary pathologist W.J. Hadlow first recognized several similarities between scrapie-a slow infection of sheep caused by an unusual infectious agent-and kuru, a fatal exotic neurodegenerative disease affecting only people of a single language group in the remote mountainous interior of New Guinea, described two years earlier by D.C. Gajdusek and V. Zigas. Based on the knowledge of scrapie, Gajdusek, C.J. Gibbs, Jr., and M.P. Alpers soon initiated efforts to transmit kuru by inoculating kuru brain tissue into non-human primates, that-although requiring several years-ultimately proved successful. In the same year that Hadlow first proposed that kuru and scrapie might have similar etiology, I. Klatzo noted that kuru's histopathology resembled that of Creutzfeldt-Jakob disease (CJD), another progressive fatal neurodegenerative disease of unknown etiology that A.M. Jakob had first described in 1921. Gajdusek and colleagues went on to demonstrate that not only the more common sporadic form of CJD but also familial CJD and a generally similar familial brain disease (Gerstmann-Sträussler-Scheinker syndrome) were also transmissible, first to non-human primates and later to other animals. (Other investigators later transmitted an even rarer brain disease, fatal familial insomnia, to animals.) Iatrogenic CJD (spread by human pituitary-derived hormones and tissue grafts) was also transmitted to animals. Much later, in 1996, a new variant of CJD was attributed to human infection with the agent of bovine spongiform encephalopathy; vCJD itself caused an iatrogenic TSE spread by blood transfusion (and probably by a human-plasma-derived clotting factor). Starting in the 1930s, the scrapie agent was found to have a unique constellation of physical properties (marked resistance to inactivation by chemicals, heat and radiation), eventually interpreted as suggesting that it might be an unconventional self-replicating pathogen based on protein and containing no nucleic acid. The work of S.B. Prusiner led to the recognition in the early 1980s that a misfolded form of a ubiquitous normal host protein was usually if not always detectable in tissues containing TSE agents, greatly facilitating the diagnosis and TSEs and understanding their pathogenesis. Prusiner proposed that the TSE agent was likely to be composed partly if not entirely of the abnormal protein, for which he coined the term "prion" protein and "prion" for the agent. Expression of the prion protein by animals-while not essential for life-was later found to be obligatory to infect them with TSEs, and a variety of mutations in the protein clearly tracked with TSEs in families, explaining the autosomal dominant pattern of disease and confirming a central role for the protein in pathogenesis. Prusiner's terminology and the prion hypothesis came to be widely though not universally accepted. A popular corollary proposal, that prions arise by spontaneous misfolding of normal prion protein leading to sporadic cases of CJD, BSE, and scrapie, is more problematic and may serve to discourage continued search for environmental sources of exposure to TSE agents.

Authors+Show Affiliations

Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States. Electronic address: David.Asher@fda.hhs.gov.Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.

Pub Type(s)

Historical Article
Journal Article
Review

Language

eng

PubMed ID

29887130

Citation

Asher, David M., and Luisa Gregori. "Human Transmissible Spongiform Encephalopathies: Historic View." Handbook of Clinical Neurology, vol. 153, 2018, pp. 1-17.
Asher DM, Gregori L. Human transmissible spongiform encephalopathies: historic view. Handb Clin Neurol. 2018;153:1-17.
Asher, D. M., & Gregori, L. (2018). Human transmissible spongiform encephalopathies: historic view. Handbook of Clinical Neurology, 153, 1-17. https://doi.org/10.1016/B978-0-444-63945-5.00001-5
Asher DM, Gregori L. Human Transmissible Spongiform Encephalopathies: Historic View. Handb Clin Neurol. 2018;153:1-17. PubMed PMID: 29887130.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human transmissible spongiform encephalopathies: historic view. AU - Asher,David M, AU - Gregori,Luisa, PY - 2018/6/12/entrez PY - 2018/6/12/pubmed PY - 2018/9/28/medline KW - Creutzfeldt–Jakob disease KW - Gerstmann–Sträussler–Scheinker syndrome KW - fatal familial insomnia KW - historic view KW - kuru KW - prion KW - scrapie KW - transmissible spongiform encephalopathy SP - 1 EP - 17 JF - Handbook of clinical neurology JO - Handb Clin Neurol VL - 153 N2 - The first of several pivotal moments leading to current understanding of human transmissible spongiform encephalopathies (TSEs) occurred in 1959 when veterinary pathologist W.J. Hadlow first recognized several similarities between scrapie-a slow infection of sheep caused by an unusual infectious agent-and kuru, a fatal exotic neurodegenerative disease affecting only people of a single language group in the remote mountainous interior of New Guinea, described two years earlier by D.C. Gajdusek and V. Zigas. Based on the knowledge of scrapie, Gajdusek, C.J. Gibbs, Jr., and M.P. Alpers soon initiated efforts to transmit kuru by inoculating kuru brain tissue into non-human primates, that-although requiring several years-ultimately proved successful. In the same year that Hadlow first proposed that kuru and scrapie might have similar etiology, I. Klatzo noted that kuru's histopathology resembled that of Creutzfeldt-Jakob disease (CJD), another progressive fatal neurodegenerative disease of unknown etiology that A.M. Jakob had first described in 1921. Gajdusek and colleagues went on to demonstrate that not only the more common sporadic form of CJD but also familial CJD and a generally similar familial brain disease (Gerstmann-Sträussler-Scheinker syndrome) were also transmissible, first to non-human primates and later to other animals. (Other investigators later transmitted an even rarer brain disease, fatal familial insomnia, to animals.) Iatrogenic CJD (spread by human pituitary-derived hormones and tissue grafts) was also transmitted to animals. Much later, in 1996, a new variant of CJD was attributed to human infection with the agent of bovine spongiform encephalopathy; vCJD itself caused an iatrogenic TSE spread by blood transfusion (and probably by a human-plasma-derived clotting factor). Starting in the 1930s, the scrapie agent was found to have a unique constellation of physical properties (marked resistance to inactivation by chemicals, heat and radiation), eventually interpreted as suggesting that it might be an unconventional self-replicating pathogen based on protein and containing no nucleic acid. The work of S.B. Prusiner led to the recognition in the early 1980s that a misfolded form of a ubiquitous normal host protein was usually if not always detectable in tissues containing TSE agents, greatly facilitating the diagnosis and TSEs and understanding their pathogenesis. Prusiner proposed that the TSE agent was likely to be composed partly if not entirely of the abnormal protein, for which he coined the term "prion" protein and "prion" for the agent. Expression of the prion protein by animals-while not essential for life-was later found to be obligatory to infect them with TSEs, and a variety of mutations in the protein clearly tracked with TSEs in families, explaining the autosomal dominant pattern of disease and confirming a central role for the protein in pathogenesis. Prusiner's terminology and the prion hypothesis came to be widely though not universally accepted. A popular corollary proposal, that prions arise by spontaneous misfolding of normal prion protein leading to sporadic cases of CJD, BSE, and scrapie, is more problematic and may serve to discourage continued search for environmental sources of exposure to TSE agents. SN - 0072-9752 UR - https://www.unboundmedicine.com/medline/citation/29887130/Human_transmissible_spongiform_encephalopathies:_historic_view_ DB - PRIME DP - Unbound Medicine ER -