title: Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores.
abstract: We previously showed that reduced infectivity of HIV with incompletely processed capsid-spacer protein 1 (CA-SP1) is rescued by cellular activation or increased expression of HSP90AB1, a member of the cytosolic heat shock protein 90 family. Here we show that HSP90AB1 is present in HIV virions and that HSP90AB1, but not nonfunctional mutated HSP90AB1(E42A+D88A), restores infectivity to HIV with mutations in CA that alter core stability. Further, the CA mutants were hypersensitive to pharmacological inhibition of HSP90AB1. In agreement with Roesch et al. (2012), we found that culturing HIV at 39.5°C enhanced viral infectivity up to 30-fold in human peripheral blood mononuclear cells (p=0.002) and rescued CA-mutant infectivity in nonactivated cells, concurrent with elevated expression of HSP90AB1 during hyperthermia. In sum, the transdominant effect of HSP90AB1 on CA-mutant HIV infectivity suggests a potential role for this class of cellular chaperones in HIV core stability and uncoating.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Pheroze
authors.initials: P
authors.lastname: Joshi
authors.forename: Barbara
authors.initials: B
authors.lastname: Sloan
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Torbett
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Stoddart
mesh_terms: D036022:Capsid Proteins / Q000235:genetics*; D002460:Cell Line; D057809:HEK293 Cells; D006678:HIV / Q000235:genetics* / Q000472:pathogenicity*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000821:virology; D009154:Mutation; D013601:T-Lymphocytes / Q000821:virology; D014758:Viral Core Proteins / Q000235:genetics
chemical_list: D036022:Capsid Proteins; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D014758:Viral Core Proteins