PMID:24098578

Citation	Tsou, YL, Lin, YW, Chang, HW, Lin, HY, Shao, HY, Yu, SL, Liu, CC, Chitra, E, Sia, C and Chow, YH (2013) Heat Shock protein 90: Role in Enterovirus 71 Entry and Assembly and Potential Target for Therapy. PLoS ONE 8:e77133
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 HSP90β siRNA or blocking HSP90 with a HSP90-specific antibody or geldanamycin (GA), a specific inhibitor of HSP90, as well as recombinant HSP90β resulted in inhibiting viral entry and subsequent viral replication. Co-immunprecipitation of EV71 with recombinant HSP90β 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.
Links	PubMed PMC3788750 Online version:10.1371/journal.pone.0077133
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:HS90B	involved_in	GO:0019062: virion attachment to host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:HS90B		GO:0016032: viral process	ECO:0000314:		P		Figure 3: RD cells transfected with Hsp90-alpha and Hsp90-beta specific siRNA. Only Hsp90-beta siRNA prevented EV71 capsid protein expression showing Hsp90-beta is involved in EV71 infection	complete CACAO 8833
HUMAN:HS90B		GO:0019062: virion attachment to host cell	ECO:0000315:		P		Figure 5B	complete CACAO 8850
HUMAN:HSPB1		GO:0046596: regulation of viral entry into host cell	ECO:0000314:		P		Figure 1	complete CACAO 8960

References

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