ETIDIOH - NEW

Abstract Background :  Highly pathogenic H5 avian influenza A has caused sporadic human infections , increasing the risk for potential human–to–human spread . In 2024, the U.S. experienced outbreaks among poultry and cattle , prompting enhanced surveillance .  Objective :  To evaluate an H5 testing algorithm in subjects with respiratory symptoms presenting for routine care during low influenza A virus circulation.  Design :  Observational study using clinical – and research–developed nucleic acid amplification tests (NAATs) and pooled screening methods.  Setting :  Academic medical center in Boston , MA.  Participants :  5,400 symptomatic individuals contributing 6,935 respiratory specimens from June 23 to August 28, 2024.  Measurements :  Specimens underwent initial respiratory pathogen testing per clinical protocols, which did not routinely include influenza due to low summer–month prevalence. Influenza A–positive specimens were s...

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...