Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid
Publication Date
September 29, 2016
Journal
PLOS Pathogens
Authors
Andrew G. Hughson, Brent Race, Allison Kraus, Laura R. Sangaré, et al
Volume
12
Issue
9
Pages
e1005914
DOI
https://dx.plos.org/10.1371/journal.ppat.1005914
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005914
Web of Science
000385621900059
Scopus
84989876009
Mendeley
http://www.mendeley.com/research/inactivation-prions-amyloid-seeds-hypochlorous-acid
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{"title"=>"Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid", "type"=>"journal", "authors"=>[{"first_name"=>"Andrew G.", "last_name"=>"Hughson", "scopus_author_id"=>"8946806000"}, {"first_name"=>"Brent", "last_name"=>"Race", "scopus_author_id"=>"6508296755"}, {"first_name"=>"Allison", "last_name"=>"Kraus", "scopus_author_id"=>"7101852305"}, {"first_name"=>"Laura R.", "last_name"=>"Sangaré", "scopus_author_id"=>"14325864300"}, {"first_name"=>"Lori", "last_name"=>"Robins", "scopus_author_id"=>"57198164484"}, {"first_name"=>"Bradley R.", "last_name"=>"Groveman", "scopus_author_id"=>"26434124000"}, {"first_name"=>"Eri", "last_name"=>"Saijo", "scopus_author_id"=>"54411415900"}, {"first_name"=>"Katie", "last_name"=>"Phillips", "scopus_author_id"=>"57195339573"}, {"first_name"=>"Luis", "last_name"=>"Contreras", "scopus_author_id"=>"57191406809"}, {"first_name"=>"Virkamal", "last_name"=>"Dhaliwal", "scopus_author_id"=>"57191413837"}, {"first_name"=>"Matteo", "last_name"=>"Manca", "scopus_author_id"=>"56190333300"}, {"first_name"=>"Gianluigi", "last_name"=>"Zanusso", "scopus_author_id"=>"6701822555"}, {"first_name"=>"Daniel", "last_name"=>"Terry", "scopus_author_id"=>"57191409128"}, {"first_name"=>"Jeffrey F.", "last_name"=>"Williams", "scopus_author_id"=>"57191404971"}, {"first_name"=>"Byron", "last_name"=>"Caughey", "scopus_author_id"=>"7006372340"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"doi"=>"10.1371/journal.ppat.1005914", "sgr"=>"84989876009", "pui"=>"612522070", "scopus"=>"2-s2.0-84989876009", "issn"=>"15537374", "pmid"=>"27685252", "isbn"=>"1553-7374 (Electronic)\r1553-7366 (Linking)"}, "id"=>"52d22161-a18d-331b-b88c-64a0aff31b74", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/inactivation-prions-amyloid-seeds-hypochlorous-acid", "reader_count"=>31, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>8, "Neuroscience"=>2, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "group_count"=>4}

Scopus | Further Information

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