Prion strain characterization of a novel subtype of Creutzfeldt-Jakob disease

Roberta Galeno, Michele Angelo Di Bari, Romolo Nonno, Franco Cardone, Marco Sbriccoli, Silvia Graziano, Loredana Ingrosso, Michele Fiorini, Angelina Valanzano, Giulia Pasini, Anna Poleggi, Ramona Vinci, Anna Ladogana, Maria Puopolo, Salvatore Monaco, Umberto Agrimi, Gianluigi Zanusso, Maurizio Pocchiari

Research output: Contribution to journalArticle

Abstract

In 2007, we reported a patient with an atypical form of Creutzfeldt- Jakob disease (CJD) heterozygous for methionine-valine (MV) at codon 129 who showed a novel pathological prion protein (PrPTSE) conformation with an atypical glycoform (AG) profile and intraneuronal PrP deposition. In the present study, we further characterize the conformational properties of this pathological prion protein (PrPTSE MVAG), showing that PrPTSE MVAG is composed of multiple conformers with biochemical properties distinct from those of PrPTSE type 1 and type 2 of MV sporadic CJD (sCJD). Experimental transmission of CJD-MVAG to bank voles and genetargeted transgenic mice carrying the human prion protein gene (TgHu mice) showed unique transmission rates, survival times, neuropathological changes, PrPTSE deposition patterns, and PrPTSE glycotypes that are distinct from those of sCJD-MV1 and sCJD-MV2. These biochemical and experimental data suggest the presence of a novel prion strain in CJD-MVAG.

Original languageEnglish
Article numbere02390-16
JournalJournal of Virology
Volume91
Issue number11
DOIs
Publication statusPublished - Jun 1 2017

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Keywords

  • Creutzfeldt-Jakob disease
  • Humanized mice
  • Prion strain
  • Prions

ASJC Scopus subject areas

  • Immunology
  • Virology

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