Abstract Influenza A virus (IAV) non-canonical replication products can be bound by host pathogen sensors , such as retinoic acid-inducible gene I (RIG-I). However, innate immune activation is infrequent in cell culture infection, in particular by adapted strains. Moreover, it is not understood why non-canonical IAV RNAs activate RIG-I in a sequence- or RNA structure-dependent manner. We therefore hypothesized that multiple errors need to occur before influenza virus RNA synthesis activates innate immune signaling . To test this idea, we investigated whether RIG-I activation is stimulated by the non-canonical or aberrant transcription of mini viral RNAs (mvRNA), a <125 nt long RNA that is overexpressed in pandemic and highly pathogenic IAV infections . Using mvRNA sequences identified in tissue culture and ferret infections , we find that mvRNAs can cause non-canonical transcription termination through a truncated 5ʹ polyadenylation signal or a 5ʹ transient RNA structure that interr...
Media Monitoring for Signals about Emerging Threats