title: Proteotoxic stress induced by Autographa californica nucleopolyhedrovirus infection of Spodoptera frugiperda Sf9 cells.
abstract: Baculovirus AcMNPV causes proteotoxicity in Sf9 cells as revealed by accumulation of ubiquitinated proteins and aggresomes in the course of infection. Inhibition of proteasomes by lactacystin increased markedly the stock of ubiquitinated proteins indicating a primary role of proteasomes in detoxication. The proteasomes were present in Sf9 cells as 26S and 20S complexes whose protease activity did not change during infection. Proteasome inhibition caused a delay in the initiation of viral DNA replication suggesting an important role of proteasomes at early stages in infection. However, lactacystin did not affect ongoing replication indicating that active proteasomes are not required for genome amplification. At late stages in infection (24-48 hpi), aggresomes containing the ubiquitinated proteins and HSP/HSC70s showed gradual fusion with the vacuole-like structures identified as lysosomes by antibody to cathepsin D. This result suggests that lysosomes may assist in protection against proteotoxicity caused by baculoviruses absorbing the ubiquitinated proteins.
authors.affiliation: NK Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow 119334, Russia.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Lyupina
authors.forename: Svetlana B
authors.initials: SB
authors.lastname: Abaturova
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Erokhov
authors.forename: Olga V
authors.initials: OV
authors.lastname: Orlova
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Beljelarskaya
authors.forename: Victor S
authors.initials: VS
authors.lastname: Mikhailov
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000235:genetics; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D009036:Moths / Q000821:virology; D017924:Nucleopolyhedroviruses; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D061987:Sf9 Cells / Q000821:virology*; D018411:Spodoptera / Q000166:cytology / Q000821:virology; D057149:Ubiquitinated Proteins / Q000378:metabolism*; D054875:Ubiquitination; D014779:Virus Replication
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004279:DNA, Viral; D050883:HSC70 Heat-Shock Proteins; D061988:Proteasome Inhibitors; D057149:Ubiquitinated Proteins; C067713:lactacystin; C025946:3-methyladenine; D046988:Proteasome Endopeptidase Complex; D000225:Adenine; D000111:Acetylcysteine