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dc.contributor.author
Booth, Laurence
dc.contributor.author
Roberts, Jane L.
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Ecroyd, Heath
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Tritsch, Sarah R.
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Bavari, Sina
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Reid, St. Patrick
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Proniuk, Stefan
dc.contributor.author
Zukiwski, Alexander
dc.contributor.author
Jacob, Abraham
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Sepúlveda, Claudia Soledad
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Giovannoni, Federico
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Garcia, Cybele
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Damonte, Elsa Beatriz
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González Gallego, Javier
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Tuñón, María J.
dc.contributor.author
Dent, Paul
dc.date.available
2018-08-16T15:30:13Z
dc.date.issued
2016-10
dc.identifier.citation
Booth, Laurence; Roberts, Jane L.; Ecroyd, Heath; Tritsch, Sarah R.; Bavari, Sina; et al.; AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication; Wiley-liss, Div John Wiley & Sons Inc; Journal of Cellular Physiology; 231; 10; 10-2016; 2286-2302
dc.identifier.issn
0021-9541
dc.identifier.uri
http://hdl.handle.net/11336/55895
dc.description.abstract
We have recently demonstrated that AR-12 (OSU-03012) reduces the function and ATPase activities of multiple HSP90 and HSP70 family chaperones. Combined knock down of chaperones or AR-12 treatment acted to reduce the expression of virus receptors and essential glucosidase proteins. Combined knock down of chaperones or AR-12 treatment inactivated mTOR and elevated ATG13 S318 phosphorylation concomitant with inducing an endoplasmic reticulum stress response that in an eIF2α—dependent fashion increased Beclin1 and LC3 expression and autophagosome formation. Over-expression of chaperones prevented the reduction in receptor/glucosidase expression, mTOR inactivation, the ER stress response, and autophagosome formation. AR-12 reduced the reproduction of viruses including Mumps, Influenza, Measles, Junín, Rubella, HIV (wild type and protease resistant), and Ebola, an effect replicated by knock down of multiple chaperone proteins. AR-12—stimulated the co-localization of Influenza, EBV and HIV virus proteins with LC3 in autophagosomes and reduced viral protein association with the chaperones HSP90, HSP70, and GRP78. Knock down of Beclin1 suppressed drug-induced autophagosome formation and reduced the anti-viral protection afforded by AR-12. In an animal model of hemorrhagic fever virus, a transient exposure of animals to low doses of AR-12 doubled animal survival from ∼30% to ∼60% and suppressed liver damage as measured by ATL, GGT and LDH release. Thus through inhibition of chaperone protein functions; reducing the production, stability and processing of viral proteins; and stimulating autophagosome formation/viral protein degradation, AR-12 acts as a broad-specificity anti-viral drug in vitro and in vivo. We argue future patient studies with AR-12 are warranted. J. Cell. Physiol. 231: 2286–2302, 2016. © 2016 Wiley Periodicals, Inc.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley-liss, Div John Wiley & Sons Inc
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Chaperones
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Antiviral
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Ar-12
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Autophagosomes
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-08-13T18:32:20Z
dc.journal.volume
231
dc.journal.number
10
dc.journal.pagination
2286-2302
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Booth, Laurence. Virginia Commonwealth University; Estados Unidos
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Fil: Roberts, Jane L.. Virginia Commonwealth University; Estados Unidos
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Fil: Ecroyd, Heath. University of Wollongong; Australia
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Fil: Tritsch, Sarah R.. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
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Fil: Bavari, Sina. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
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Fil: Reid, St. Patrick. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
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Fil: Proniuk, Stefan. Arno Therapeutics; Estados Unidos
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Fil: Zukiwski, Alexander. Arno Therapeutics; Estados Unidos
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Fil: Jacob, Abraham. University of Arizona; Estados Unidos
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Fil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Giovannoni, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: González Gallego, Javier. Universidad de León; España
dc.description.fil
Fil: Tuñón, María J.. Universidad de León; España
dc.description.fil
Fil: Dent, Paul. Virginia Commonwealth University; Estados Unidos
dc.journal.title
Journal of Cellular Physiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1002/jcp.25431
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.25431


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