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Kuru, the First Human Prion Disease viruses Review Kuru, the First Human Prion Disease † 1, 2 1 3 PawePawełł P. LiberskiLiberski 1,*,* Agata, Agata Gajos Gajos 2, Beata, Beata Sikorska Sikorska 1 and Shirleyand Shirley Lindenbaum Lindenbaum 3 1 1 LaboratoryLaboratory of of Electron Electron Microscopy Microscopy and and Neurop Neuropathology,athology, Department Department of of Molecular Molecular Pathology Pathology and and Neuropathology,Neuropathology, Medical Medical University University Lodz, Lodz, 90-419 90-419 Lodz, Lodz, Poland; Poland; [email protected] [email protected] 2 Department of Extrapyramidal Diseases, Medical University of Lodz, 90-419 Lodz, Poland; 2 Department of Extrapyramidal Diseases, Medical University of Lodz, 90-419 Lodz, Poland; [email protected] [email protected] 3 Department of Anthropology, Graduate Center, City University of New York, New York, NY 10016, USA; 3 Department of Anthropology, Graduate Center, City University of New York, New York, NY 10016, USA; [email protected] [email protected] * Correspondence: [email protected] * Correspondence: [email protected] † This paper is dedicated to late Daniel Carleton Gajdusek (1923–2008). † This paper is dedicated to late Daniel Carleton Gajdusek (1923–2008). Received: 1 February 2019; Accepted: 1 March 2019; Published: date 7 March 2019 Abstract: Kuru,Kuru, the the first first human prion disease was tran transmittedsmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In In this this review, review, we we summar summarizeize the the history history of of this this seminal discovery, its anthropological background,background, epidemiology, epidemiology, clinical clinical picture, picture, neuropathology, neuropathology, and molecular and molecular genetics. Wegenetics. provide We descriptions provide descriptions of electron of microscopyelectron micr andoscopy confocal and confocal microscopy microscopy of kuru amyloidof kuru amyloid plaques plaquesretrieved retrieved from a paraffin-embedded from a paraffin-embedded block of anbloc oldk of kuru an case,old kuru named case, Kupenota. named Kupenota. The discovery The discoveryof kuru opened of kuru new opened vistas ofnew human vistas medicine of huma andn medicine was pivotal and in was the subsequentpivotal in the transmission subsequent of transmissionCreutzfeldt–Jakob of Creutzfeldt–Jakob disease, as well as disease, the relevance as well that as bovine the relevance spongiform that encephalopathy bovine spongiform had for encephalopathytransmission to humans. had for transmission The transmission to humans. of kuru wasThe onetransmission of the greatest of kuru contributions was one of to the biomedical greatest contributionssciences of the to 20th biomedical century. sciences of the 20th century. Keywords: Kuru; prion diseases; neuropathology; Carleton Gajdusek 1. Introduction “Kuru”, the first first prion disease, was discovered by D. Carleton GajdusekGajdusek (Figure(Figure1 1))[ 1[1–11].–11]. Figure 1.Figure Dr. D. 1. CarletonDr. D. Carleton Gajdusek Gajdusek (lhr-57-ng-332) (lhr-57-ng-332).. Courtesy Courtesy of D. Carleton of D. Carleton Gajdusek. Gajdusek. Viruses 2019,, 11,, 232;x; doi: doi: FOR10.3390/v11030232 PEER REVIEW www.mdpi.com/journal/viruseswww.mdpi.com/journal/viruses Viruses 2019, 11, 232 2 of 25 Viruses 2019, 11, x FOR PEER REVIEW 2 of 24 It was also the firstfirst humanhuman prion diseasedisease transmitted to chimpanzees and was classified classified as “a transmissible spongiform encephalopathy” (TSE), or slow unconventional virus disease. It was first first reported in two publications by Gajdusek andand VincentVincent ZigasZigas inin 19571957 (Figure(Figure2 2))[ 12[12,13].,13]. Figure 2. Dr. Vin Zigas (dcg-57-ng-336). Cour Courtesytesy of D. Carleton Gajdusek. The definitiondefinition ofof kurukuru asas bothboth neurodegenerative neurodegenerative (not (not inflammatory) inflammatory) and and infectious infectious [14 [14,15],15] led led to tosubsequent subsequent transmission transmission of Creutzfeldt–Jakob of Creutzfeldt–Jako diseaseb disease (CJD) [ 16(CJD)] and suggested[16] and suggested that kuru represents that kuru a representsnovel class a of novel diseases class caused of diseases by a novel caused class by of a pathogensnovel class called of pathogens prions. Kurucalled won prions. a Nobel Kuru prize won for a NobelGajdusek prize in 1976for Gajdusek and, indirectly, in 1976 as and, he discoveredindirectly, “prions”,as he discovered for Stanley “prions”, B. Prusiner for Stanley in 1997. B. Kuru Prusiner was inlinked, 1997. also Kuru indirectly, was linked, to a also third indirectly, Nobel Prize to a for third Kurt Nobel Wüthrich, Prize for who Kurt determined Wüthrich, the who structure determined of the prionthe structure protein of [17 the]. Asprion Gajdusek protein emphasized[17]. As Gajdusek for the emphasized last time in for his the life la atst thetime Royal in his Society life at the meeting Royal Societyon kuru meeting in 2007 [on18 ],kuru the researchin 2007 [18], on kuru the research advanced on the kuru ideas advanced of molecular the ideas casting, of molecular dermatoglyphics, casting, dermatoglyphics,osmium shadowing osmium in electron shadowing microscopy, in electron and amyloid-enhancing microscopy, and amyloid-enhancing factors. Kuru research factors. impacted Kuru researchthe concepts impacted of nucleation–polymerization the concepts of nucleation–polymerization and led to an idea of and conformational led to an idea disorders of conformational [19–21] or prionoidsdisorders [19–21] [22]. or prionoids [22]. 2. Background and Ethnographic Setting “Kuru”, in the Fore language (Figures 33 andand4 ),4), means means to to tremble tremble from from fever fever or or cold cold [ [23–36]:23–36]: “The“The nativesnatives ofof almostalmost all all of of the the Fore Fore hamlets hamlets have have stated stated that that it hasit has been been present present for for a ‘long a ‘long time’, time’, but butthey they soon soon modify modify to mean to mean that that in recent in recent years year it hass it becomehas become an increasingly an increasingly severe severe problem problem and thatand thatin the in early the early youth youth of our of oldestour oldest informants informants there there was nowas kuru no kuru at all” at [all”15]. [15]. Viruses 2019, 11, 232 3 of 25 Viruses 2019,, 11,, xx FORFOR PEERPEER REVIEWREVIEW 3 of 24 Figure 3. AA general general view view of of a Fore hamlet. A A kuru kuru victim victim is is sitting sitting in in the the first first row between two supporters (dcg-ng-bw-12). Courtesy of D. Carleton Gajdusek. Figure 4. AA general general view of a Fore hamlet (dcg-57-ng (dcg-57-ng-186).-186).-186). CourtesyCourtesy ofof D.D. CarletonCarleton Gajdusek. Gajdusek. The disease was confined confined to natives of the Fore linguistic group in Papua New Guinea’s Eastern Highlands andand neighboring neighboring linguistic linguistic groups groups (Auiana, (Auiana, Awa, Awa, Usurufa, Usurufa, Kanite, Kanite, Keiagana, Keiagana, Iate, Kamano, Iate, Kamano,and Gimi). and The Gimi). Fore The reports Fore suggested reports suggested that kuru that first kuru appeared first appeared at Uwami, at a Uwami, Keiagana a villageKeiagana to villagethe northwest, to the northwest, around 1900, around and 1900, then and in then the North in the North Fore around Fore around 1920. 1920. It then It then traveled traveled down down the thesoutheastern southeastern border, border, arriving arriving at Wanitabe at Wanitabe in the in central the central South ForeSouth by Fore 1930. by From 1930. Wanikanto, From Wanikanto, where it whereappeared it appeared in 1927, it in turned 1927, towardit turned the toward northwest, the no torthwest, Miarasa to and Miarasa Paigata. and The Paigata. first cases Theat first Purosa, cases six at Purosa,miles south six ofmiles Wanitabe, south appearedof Wanitabe, in the appeared 1930s, and, in inthe some 1930s, southwestern and, in some and southeasternsouthwestern areas, and southeasternit arrived as lateareas, as it the arrived 1940s as (see late map as the [37 1940s]). Zigas (see map and Gajdusek[37]). Zigas [38 and] noticed Gajdusek that, [38] when noticed the that, Fore whenpeople the at KasaraiFore people moved at Kasarai temporarily moved to livetemporarily with the to Yar live people with andthe Yar settled people there and for settled about athere decade, for aboutkuru casesa decade, still kuru occurred. cases still As Lindenbaumoccurred. As Lindenba observedum [39 observed], the Fore [39], descriptions the Fore descriptionsdescriptions of their encounter ofof theirtheir encounterwith the new with disease the new were disease rich in were detail. rich It in is detail. now thought It isis nownow that thoughtthought kuru first thatthatarose kurukuru infirstfirst asingle arosearose individualinin aa singlesingle individualfromindividual a spontaneous fromfrom aa spontaneousspontaneous change that changechange created thatthat a pathogenic, createdcreated aa pathogenic,pathogenic, infectious agentinfectiousinfectious in the agentagent brain, inin inthethe the brain,brain, same inin way thethe samethat sporadic way that Creutzfeldt–Jakob sporadic Creutzfeldt–Jakob disease occurs. disease The occurs. recycling The of recycling the infectious of the agent infectious through agent the throughconsumption the consumption of deceased of relatives deceased amplified relatives the ampl agentifiedified and thethethe agentagent disease andand thethe in the diseasedisease community, inin
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