Generation of recombinant pandemic H1N1 influenza virus with the HA cleavable by bromelain and identification of the residues influencing HA bromelain cleavage

► We found that the HA of 2009 H1N1 A/CA/09 virus could not be cleaved by bromelain for antiserum production. ► We generated a chimeric virus to make the HA cleavable by bromelain. ► We demonstrated that chimeric HA was immunogenic and protective. ► We determined the molecular mechanism of HA cleavage. ► We showed that amino acids at positions 373 and 374 of the HA are critical for HA bromelain cleavage.