title: Sendai virus trailer RNA simultaneously blocks two apoptosis-inducing mechanisms in a cell type-dependent manner.
abstract: Induction of apoptosis during Sendai virus (SeV) infection has previously been documented to be triggered by initiator caspases (for strain F) or by a contribution of the cellular protein TIAR (T-cell-activated intracellular antigen-related) (for strain Z). Here, evidence was provided that both TIAR and caspases are simultaneously involved in apoptosis induction as a result of infection with SeV strain F. SeV F infection induced death in all tested cell lines, which could only be partially prevented through the pan-caspase inhibitor z-VAD-fmk. However, infection of seven different cell lines with the SeV mutant Fctr48z overexpressing a TIAR-sequestering RNA from the modified leader resulted in a cell type-dependent reduced cytopathic effect (CPE); in an earlier study a similar mutant derived from SeV Z was shown to prevent the induction of any CPE. Finally, blocking of caspases through z-VAD-fmk combined with Fctr48z infection led to complete abrogation of CPE, clearly demonstrating the existence of two separate mechanisms inducing cell death during SeV F infections. Interestingly, a cell type-specific interference between these two mechanisms could be detected during infection with the mutant virus Fctr48z: RNA transcribed from the mutated leader was able to trans-dominantly inhibit caspase-mediated apoptosis. Thus, virus-expressed factors enabling a well-balanced ratio of suppression and triggering of apoptosis seem to be essential for optimal virus replication.
authors: Department of Molecular Virology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors: Marian
authors: M
authors: Wiegand
authors: Department of Molecular Virology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors: Sascha
authors: S
authors: Bossow
authors: Department of Molecular Virology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors: Wolfgang J
authors: WJ
authors: Neubert
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D006801:Humans; D009154:Mutation; D009928:Organ Specificity; D012367:RNA, Viral; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D010253:Respirovirus Infections / Q000821:virology; D029082:Sendai virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C076751:TIAL1 protein, human; D020169:Caspases