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.