Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid

PLoS Pathogens

Jeffrey F. Williams¹  Daniel Terry¹  Laura R. Sangaré²  Gianluigi Zanusso³  Virkamal Dhaliwal⁴  Luis Contreras⁴  Lori Robins⁴  Byron Caughey⁵  Matteo Manca⁵  Andrew G. Hughson⁵  Katie Phillips⁵  Allison Kraus⁵  Bradley R. Groveman⁵  Eri Saijo⁵  Brent Race⁵ 

[1] Briotech Inc., Woodinville, Washington, United States of America;Department of Epidemiology, University of Washington, Seattle, Washington, United States of America;Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico G.B. Rossi, University of Verona, Verona, Italy;Department of Physical Sciences, University of Washington, Bothell, Washington, United States of America;Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana, United States of America

关键词: Prions;    Animal prion diseases;    Scrapie;    Hamsters;    Creutzfeldt-Jakob disease;    Hypochlorites;    Amyloid proteins;    Stainless steel;   

DOI  :  10.1371/journal.ppat.1005914

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Hypochlorous acid (HOCl) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH ≥~12) sodium hypochlorite bleach, ≥1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl) that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC) assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of ≥103- to 106-fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of ≥~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion protein. BrioHOCl treatments had similar effects on amyloids composed of human α-synuclein and a fragment of human tau. These results indicate that HOCl can block the self-propagating activity of prions and other amyloids.

【 授权许可】

CC BY