Pubblicazioni

Autori:

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

Titolo:

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

Anno:

2017

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

Sì

Nome rivista:

Journal of Virology

ISSN Rivista:

0022-538X

N° Volume:

91

Numero o Fascicolo:

11

Intervallo pagine:

1-12

Parole chiave:

Creutzfeldt-Jakob disease; humanized mice; prion strain; prions

Breve descrizione dei contenuti:

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 (PrP(TSE)) conformation with an atypical glycoform (AG) profile and an intraneuronal PrP deposition. In the present study, we further characterized the conformational properties of this pathological prion protein (PrP(TSE) MV(AG)) showing that PrP(TSE) MV(AG) is composed by multiple conformers with biochemical properties distinct from PrP(TSE) type 1 and type 2 of MV sporadic CJD (sCJD). Experimental transmission of CJD-MV(AG) to bank voles and gene-targeted transgenic mice carrying the human prion protein gene (TgHu) showed unique transmission rates, survival times, neuropathological changes, PrP(TSE) deposition patterns and PrP(TSE) glycotypes that are distinct from sCJD-MV1 and sCJD-MV2. These biochemical and experimental data suggest the presence of a novel prion strain in CJD-MV(AG)IMPORTANCE Sporadic Creutzfeldt-Jakob disease is caused by the misfolding of the cellular prion protein, which assumes two major different conformations (type 1 and type 2) and, together with the methionine/valine polymorphic codon 129 of the prion protein gene, contribute to the occurrence of distinct clinical-pathological phenotypes. Inoculation in laboratory rodents of brain tissues from the six possible combination of pathological prion protein type with codon 129 genotypes results in the identification of 3 to 4 strains of prions. We report on the identification of a novel strain of Creutzfeldt-Jakob disease isolated from a patient who carried an abnormally glycosylated pathological prion protein. This novel strain has unique biochemical characteristics, does not transmit to humanized transgenic mice, and shows exclusive transmission properties in bank voles. The identification of a novel human prion strain improves our understanding on the pathogenesis of the disease and on possible mechanisms of prion transmission.

Pagina Web:

https://doi.org/10.1128/JVI.02390-16

Id prodotto:

98248

Handle IRIS:

11562/965651

ultima modifica:

30 novembre 2022

Citazione bibliografica:

Galeno, Roberta; Di Bari, Michele Angelo; Nonno, Romolo; Cardone, Franco; Sbriccoli, Marco; Graziano, Silvia; Ingrosso, Loredana; Fiorini, Michele; Valanzano, Angelina; Pasini, Giulia; Poleggi, Anna; Vinci, Ramona; Ladogana, Anna; Puopolo, Maria; Monaco, Salvatore; Agrimi, Umberto; Zanusso, Gianluigi; Pocchiari, Maurizio, Prion strain characterization of a novel subtype of Creutzfeldt-Jakob disease «Journal of Virology» , vol. 91 , n. 11 , 2017 , pp. 1-12

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo