Sendai virus defective-interfering genomes and the activation of interferon-beta

Abstract

The ability of some Sendai virus stocks to strongly activate IFNβ has long been known to be associated with defective-interfering (DI) genomes. We have compared SeV stocks containing various copyback and internal deletion DI genomes (and those containing only nondefective (ND) genomes) for their ability to activate reporter genes driven by the IFNβ promoter. We found that this property was primarily due to the presence of copyback DI genomes and correlated with their ability to self-anneal and form dsRNA. The level of IFNβ activation was found to be proportional to that of DI genome replication and to the ratio of DI to ND genomes during infection. Over-expression of the viral V and C proteins was as effective in blocking the copyback DI-induced activation of the IFNβ promoter as it was in reducing poly-I/C-induced activation, providing evidence that these DI infections activate IFNβ via dsRNA. Infection with an SeV stock that is highly contaminated with copyback DI genomes is thus a very particular way of potently activating IFNβ, presumably by providing plentiful dsRNA under conditions of reduced expression of viral products which block the host antiviral response.