title: BiP and multiple DNAJ molecular chaperones in the endoplasmic reticulum are required for efficient simian virus 40 infection.
abstract: Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infection was specifically inhibited by up to 50-fold by knockdown of four different DNAJ molecular cochaperones or by inhibition of BiP, the Hsp70 partner of DNAJB11. These proteins were not required for the initiation of capsid disassembly, but knockdown markedly inhibited SV40 exit from the ER. In addition, BiP formed a complex with SV40 capsids in the ER in a DNAJB11-dependent fashion. These experiments identify five new cellular proteins required for SV40 infection and suggest that the binding of BiP to the capsid is required for ER exit. Further studies of these proteins will provide insight into the molecular mechanisms of polyomavirus infection and ER function.
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Goodwin
authors.forename: Alex
authors.initials: A
authors.lastname: Lipovsky
authors.forename: Takamasa
authors.initials: T
authors.lastname: Inoue
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Magaldi
authors.forename: Anne P B
authors.initials: AP
authors.lastname: Edwards
authors.forename: Kristin E Y
authors.initials: KE
authors.lastname: Van Goor
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Paton
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Atwood
authors.forename: Billy
authors.initials: B
authors.lastname: Tsai
authors.forename: Daniel
authors.initials: D
authors.lastname: DiMaio
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism / Q000821:virology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D013539:Simian virus 40 / Q000472:pathogenicity*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones