#Haemagglutinin 162-164 #deletions enhance #influenza B/Victoria virus #fitness and #virulence in vivo
Abstract Influenza B viruses cause substantial respiratory disease and seasonal outbreaks. Despite decades of circulation in humans , only the B/Victoria lineage persisted after the COVID-19 pandemic. Continual evolution has generated hemagglutinin deletion variants at residues 162-164 that drive successive epidemics , yet their functional consequences remain poorly understood. Using integrated phylodynamics and reverse genetics , we show that Clade V1A.1 viruses carrying a two-amino acid deletion exhibit enhanced replication and increased virulence compared with ancestral viruses lacking deletions. The recently prevailing Clade V1A.3 , which harbors a three-amino acid deletion together with the K136E substitution, has completely displaced V1A.1 and causes more severe disease in mice . Both clades bound efficiently to alpha 2-3 and 2-6 sialylated glycans and exhibited broad tolerance to acidic pH and elevated temperatures . These findings reveal that specific combinations of HA d...