title: Influenza virus infection induces the nuclear relocalization of the Hsp90 co-chaperone p23 and inhibits the glucocorticoid receptor response.
abstract: The genomic RNAs of influenza A viruses are associated with the viral polymerase subunits (PB1, PB2, PA) and nucleoprotein (NP), forming ribonucleoprotein complexes (RNPs). Transcription/replication of the viral genome occurs in the nucleus of infected cells. A role for Hsp90 in nuclear import and assembly of newly synthetized RNA-polymerase subunits has been proposed. Here we report that the p23 cochaperone of Hsp90, which plays a major role in glucocorticoid receptor folding and function, associates with influenza virus polymerase. We show that p23 is not essential for viral multiplication in cultured cells but relocalizes to the nucleus in influenza virus-infected cells, which may alter some functions of p23 and Hsp90. Moreover, we show that influenza virus infection inhibits glucocorticoid receptor-mediated gene transactivation, and that this negative effect can occur through a p23-independent pathway. Viral-induced inhibition of the glucocorticoid receptor response might be of significant importance regarding the physiopathology of influenza infections in vivo.
authors.affiliation: Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, Département de Virologie, Paris, France.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Ge
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Rameix-Welti
authors.forename: Elyanne
authors.initials: E
authors.lastname: Gault
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chase
authors.forename: Emmanuel
authors.initials: E
authors.lastname: dos Santos Afonso
authors.forename: Didier
authors.initials: D
authors.lastname: Picard
authors.forename: Martin
authors.initials: M
authors.lastname: Schwemmle
authors.forename: Nadia
authors.initials: N
authors.lastname: Naffakh
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004285:Dogs; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D006801:Humans; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology*; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000201:enzymology / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000821:virology; D010750:Phosphoproteins / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D011485:Protein Binding; D021381:Protein Transport; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014779:Virus Replication / Q000502:physiology
chemical_list: D018832:Molecular Chaperones; D010750:Phosphoproteins; D011965:Receptors, Glucocorticoid; D012321:DNA-Directed RNA Polymerases; D019746:Intramolecular Oxidoreductases; C490849:PTGES3 protein, human; D000071876:Prostaglandin-E Synthases