Agent strain variation in human prion disease: Insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease

Piero Parchi, Maura Cescatti, Silvio Notari, Walter J. Schulz-Schaeffer, Sabina Capellari, Armin Giese, Wen Quan Zou, Hans Kretzschmar, Bernardino Ghetti, Paul Brown

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Six clinico-pathological phenotypes of sporadic Creutzfeldt-Jakob disease have been characterized which correlate at the molecular level with the type (1 or 2) of the abnormal prion protein, PrPTSE, present in the brain and with the genotype of polymorphic (methionine or valine) codon 129 of the prion protein gene. However, to what extent these phenotypes with their corresponding molecular combinations (i.e. MM1, MM2, VV1 etc.) encipher distinct prion strains upon transmission remains uncertain. We studied the PrPTSE type and the prion protein gene in archival brain tissues from the National Institutes of Health series of transmitted Creutzfeldt-Jakob disease and kuru cases, and characterized the molecular and pathological phenotype in the affected non-human primates, including squirrel, spider, capuchin and African green monkeys. We found that the transmission properties of prions from the common sporadic Creutzfeldt-Jakob disease MM1 phenotype are homogeneous and significantly differ from those of sporadic Creutzfeldt-Jakob disease VV2 or MV2 prions. Animals injected with iatrogenic Creutzfeldt-Jakob disease MM1 and genetic Creutzfeldt-Jakob disease MM1 linked to the E200K mutation showed the same phenotypic features as those infected with sporadic Creutzfeldt-Jakob disease MM1 prions, whereas kuru most closely resembled the sporadic Creutzfeldt-Jakob disease VV2 or MV2 prion signature and neuropathology. The findings indicate that two distinct prion strains are linked to the three most common Creutzfeldt-Jakob disease clinico-pathological and molecular subtypes and kuru, and suggest that kuru may have originated from cannibalistic transmission of a sporadic Creutzfeldt-Jakob disease of the VV2 or MV2 subtype.

Original languageEnglish
Pages (from-to)3030-3042
Number of pages13
JournalBrain
Volume133
Issue number10
DOIs
Publication statusPublished - 2010

Fingerprint

Prion Diseases
Prions
National Institutes of Health (U.S.)
Kuru
Creutzfeldt-Jakob Syndrome
Phenotype
Cercopithecus aethiops
Sciuridae
Spiders
Brain
Valine
Codon
Methionine
Primates
Genes
Sporadic Creutzfeldt-Jakob Disease
Genotype
Mutation
Prion Proteins

Keywords

  • neurodegenerative disorders
  • neuropathology
  • phenotype
  • prion diseases
  • strain typing

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Agent strain variation in human prion disease : Insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease. / Parchi, Piero; Cescatti, Maura; Notari, Silvio; Schulz-Schaeffer, Walter J.; Capellari, Sabina; Giese, Armin; Zou, Wen Quan; Kretzschmar, Hans; Ghetti, Bernardino; Brown, Paul.

In: Brain, Vol. 133, No. 10, 2010, p. 3030-3042.

Research output: Contribution to journalArticle

Parchi, Piero ; Cescatti, Maura ; Notari, Silvio ; Schulz-Schaeffer, Walter J. ; Capellari, Sabina ; Giese, Armin ; Zou, Wen Quan ; Kretzschmar, Hans ; Ghetti, Bernardino ; Brown, Paul. / Agent strain variation in human prion disease : Insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease. In: Brain. 2010 ; Vol. 133, No. 10. pp. 3030-3042.
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