國家衛生研究院 NHRI:Item 3990099045/7582

NHRI > National Institute of Infectious Diseases and Vaccinology > Joe Yen-Hung Chow > Periodical Articles > Item 3990099045/7582

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Title:	Heat Shock protein 90: Role in enterovirus 71 entry and assembly and potential target for therapy
Authors:	Tsou, YL;Lin, YW;Chang, HW;Lin, HY;Shao, HY;Yu, SL;Liu, CC;Chitra, E;Sia, C;Chow, YH
Contributors:	Division of Vaccine Research and Development
Abstract:	Although several factors participating in enterovirus 71 (EV71) entry and replication had been reported, the precise mechanisms associated with these events are far from clear. In the present study, we showed that heat shock protein 90 (HSP90) is a key element associated with EV71 entry and replication in a human rhabdomyosarcoma of RD cells. Inhibition of HSP90 by pretreating host cells with HSP90beta siRNA or blocking HSP90 with a HSP90-specific antibody or geldanamycin (GA), a specific inhibitor of HSP90, as well as recombinant HSP90beta resulted in inhibiting viral entry and subsequent viral replication. Co-immunprecipitation of EV71 with recombinant HSP90beta and colocalization of EV71-HSP90 in the cells demonstrated that HSP90 was physically associated with EV71 particles. HSP90 seems to mediate EV71 replication by preventing proteosomal degradation of the newly synthesized capsid proteins, but does not facilitate viral gene expression at transcriptional level. This was evident by post-treatment of host cells with GA, which did not affect the expression of viral transcripts but accelerated the degradation of viral capsid proteins and interfered with the formation of assembled virions. In vivo studies were carried out using human SCARB2-transgenic mice to evaluate the protection conferred by HSP90 inhibitor, 17-allyamino-17-demethoxygeldanamycin (17-AAG), an analog of geldanamycin, that elicited similar activity but with less toxicity. The results showed that the administration of 17-AAG twice conferred the resistance to hSCARB2 mice challenged with C2, C4, and B4 genotypes of EV71. Our data supports HSP90 plays an important role in EV71 infection. Targeting of HSP90 with clinically available drugs might provide a feasible therapeutic approach to treat EV71 infection.
Date:	2013-10-02
Relation:	PLoS ONE. 2013 Oct 2;8(10):Article number e77133.
Link to:	http://dx.doi.org/10.1371/journal.pone.0077133
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000325434500095
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84884863066
Appears in Collections:	[Joe Yen-Hung Chow] Periodical Articles [Charles Dwo-Yuan Sia(2006-2014)] Periodical Articles [Chia-Chyi Liu] Periodical Articles

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