title: Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly.
abstract: Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone.
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan. yuwang@mail.cgu.edu.tw
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Wang
authors.forename: Rei-Lin
authors.initials: RL
authors.lastname: Kuo
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Ma
authors.forename: Hsing-I
authors.initials: HI
authors.lastname: Huang
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.forename: Sih-Min
authors.initials: SM
authors.lastname: Yen
authors.forename: Chi-Ruei
authors.initials: CR
authors.lastname: Huang
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
mesh_terms: D016227:Benzoquinones; D045744:Cell Line, Tumor; D002499:Centrifugation, Density Gradient; D029821:Enterovirus A, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004769:Enterovirus Infections / Q000821:virology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047029:Lactams, Macrocyclic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D034622:RNA Interference; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000378:metabolism*; D019065:Virus Assembly / Q000187:drug effects*; D014779:Virus Replication
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011506:Proteins; D014764:Viral Proteins; C001277:geldanamycin
keywords: Enterovirus 71; Geldanamycin; Heat shock protein 90; Hsp90β; Viral particles assembly