title: Cell-specific inhibition of paramyxovirus maturation by proteasome inhibitors.
abstract: Effects of proteasome inhibitors on the replication of a paramyxovirus in comparison with the effects on replication of an orthomyxovirus and rhabdovirus were investigated. Treatment of Sendai virus (SeV)-infected LLC-MK2 cells with 50 microM MG132 reduced virus growth to ca. 1/10,000, and treatment with different concentrations of MG132 reduced virus growth in a dose-dependent manner. Released amounts of viral proteins were reduced in correspondence with decrease in infectivity. The inhibition of virus maturation was confirmed by an SeV-like particle formation system. Lactacystin also impaired SeV growth and zLL impaired the growth to a lesser extent, suggesting involvement of proteasomes in the restriction of virus growth. In the presence of MG132, localizations of the M protein and viral F and HN glycoproteins on the cell membrane appeared to be partly dissociated, although the viral glycoproteins were normally transported to the cell surface. These results suggest that an early step of SeV assembly was disturbed by proteasome inhibitors. The relationship of the results with ubiquitin is also discussed. SeV maturation was less susceptible and resistant to MG132 in CV1 cells and A549 cells, respectively, indicating cell specificity of the drug effect. Release of vesicular stomatitis virus also showed high susceptibility to MG132 and release of influenza virus A/WSN/33 was only mildly susceptible to the drug in LLC-MK2 cells. Effects of proteasome inhibitors on virus maturation are thus highly cell-specific and partly virus-specific.
authors.affiliation: Department of Virology, Graduate School of Biomedical Sciences, Hiroshima University 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yukie
authors.initials: Y
authors.lastname: Shimazu
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugahara
authors.forename: Masaru
authors.initials: M
authors.lastname: Kuwayama
authors.forename: Akira
authors.initials: A
authors.lastname: Hiramatsu
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kiyotani
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takemasa
authors.initials: T
authors.lastname: Sakaguchi
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015707:HN Protein / Q000378:metabolism; D009980:Influenza A virus / Q000187:drug effects / Q000254:growth & development; D007976:Leupeptins / Q000494:pharmacology*; D008253:Macaca mulatta; D008264:Macrophages / Q000821:virology; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000254:growth & development; D010252:Paramyxoviridae / Q000187:drug effects* / Q000254:growth & development; D061988:Proteasome Inhibitors; D012209:Rhabdoviridae / Q000187:drug effects / Q000254:growth & development; D029082:Sendai virus / Q000187:drug effects / Q000254:growth & development; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000254:growth & development; D014760:Viral Fusion Proteins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism; D019065:Virus Assembly / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D015707:HN Protein; D007976:Leupeptins; D061988:Proteasome Inhibitors; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins; C067713:lactacystin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine