Transmission Characteristics of Variably Protease-Sensitive Prionopathy

Details

• Alternative Title:
  Emerg Infect Dis
• Personal Author:
  Notari, Silvio ; Xiao, Xiangzhu ; Espinosa, Juan Carlos ; Cohen, Yvonne ; Qing, Liuting ; Aguilar-Calvo, Patricia ; Kofskey, Diane ; Cali, Ignazio ; Cracco, Laura ; Kong, Qingzhong ; Torres, Juan Maria ; Zou, Wenquan ; Gambetti, Pierluigi
• Description:
  Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS. The VPSPr atypical features raised the issue of transmissibility, a prototypical property of prion diseases. We inoculated VPSPr brain homogenate into transgenic mice expressing various levels of human PrP (PrP(C)). On first passage, 54% of challenged mice showed histopathologic lesions, and 34% harbored abnormal PrP similar to that of VPSPr. Surprisingly, no prion disease was detected on second passage. We concluded that VPSPr is transmissible; thus, it is an authentic prion disease. However, we speculate that normal human PrP(C) is not an efficient conversion substrate (or mouse brain not a favorable environment) and therefore cannot sustain replication beyond the first passage.
• Subjects:
  Humans Prions And Related Diseases Research Transgenic Mice Transmissibility Transmission Characteristics Of Variably Protease-Sensitive Prionopathy VPSPr
• Source:
  Emerg Infect Dis. 20(12):2006-2014.
• Document Type:
  Journal Article
• Volume:
  20
• Issue:
  12
• Collection(s):
  Emerging Infectious Diseases
• Main Document Checksum:
  urn:sha256:7c751852863196a86e331f47582878ad0c415116cdda5cf91631e33535b60753
• Download URL:
  https://stacks.cdc.gov/view/cdc/26359/cdc_26359_DS1.pdf
• File Type:
  [PDF - 607.81 KB ]