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Acid inactivation of prions: efficient at elevated temperature or high acid concentration

¹ IMB, Leibniz Institut für Molekulare Biotechnologie Jena eV, Jena, Germany
² Institut für Physikalische Biologie, Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-Universität Düsseldorf, Gebäude 26.12, D-40225 Düsseldorf, Germany
³ Friedrich-Löffler-Institut, Greifswald Insel Riems, Germany
⁴ Robert Koch-Institut, P24-TSE, Berlin, Germany

Correspondence
Detlev Riesner
riesner{at}biophys.uni-duesseldorf.de

Scrapie prion rods isolated from hamster and non-infectious aggregates of the corresponding recombinant protein rPrP(90–231) were incubated with hydrochloric acid. The amount of PrP and of infectivity that survived incubation in HCl at varying times, acid concentrations and temperatures was quantified by Western blot densitometry and bioassays, respectively. Prion rods and rPrP aggregates showed similar HCl hydrolysis kinetics of PrP, indicating structural homology. For 1 M HCl and 25 °C, the rate of PrP hydrolysis follows first-order kinetics at 0·014 h^–1; the rate of infectivity inactivation is 0·54 h^–1. Hydrolysis for 1 h at 25 °C was only slightly proportional to HCl concentration up to 5 M, but complete loss of infectivity and PrP reduction to <2 % was observed at 8 M HCl. The temperature dependence of unhydrolysed PrP, as well as infectivity at 1 M HCl for 1 h, showed a slight decrease up to 45 °C, but a sigmoidal decrease by several orders of magnitude at higher temperatures. The slow hydrolysis of PrP and inactivation of infectivity by acid treatment at room temperature are attributed to solvent inaccessibility of prion rods and rPrP aggregates, respectively. The more effective hydrolysis and inactivation at temperatures above 45 °C are interpreted as thermally induced disaggregation with an activation energy of 50–60 kJ mol^–1. Most importantly, infectivity was always inactivated faster or to a higher extent than PrP was hydrolysed at several incubation times, HCl concentrations and temperatures.

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