Pathogenic influenza B virus in the ferret model establishes lower respiratory tract infection

Influenza B viruses have become increasingly more prominent during influenza seasons. Influenza B infection is typically considered a mild disease and receives less attention than influenza A, but has been causing 20 to 50% of the total influenza incidence in several regions around the world. Although there is increasing evidence of mid to lower respiratory tract diseases such as bronchitis and pneumonia in influenza B patients, little is known about the pathogenesis of recent influenza B viruses. Here we investigated the clinical and pathological profiles of infection with strains representing the two current co-circulating B lineages (B/Yamagata and B/Victoria) in the ferret model. Specifically, we studied two B/Victoria (B/Brisbane/60/2008 and B/Bolivia/1526/2010) and two B/Yamagata (B/Florida/04/2006 and B/Wisconsin/01/2010) strain infections in ferrets and observed strain-specific but not lineage-specific pathogenicity. We found B/Brisbane/60/2008 caused the most severe clinical illness and B/Brisbane/60/2008 and the B/Yamagata strains instigated pathology in the middle to lower respiratory tract. Importantly, B/Brisbane/60/2008 established efficient lower respiratory tract infection with high viral burden. Our phylogenetic analyses demonstrate profound reassortment among recent influenza B viruses, which indicates the genetic make-up of B/Brisbane/60/2008 differs from the other strains. This may explain the pathogenicity difference post-infection in ferrets.