title: The H5N1 influenza variant Fujian-like hemagglutinin selected following vaccination exhibits a compromised furin cleavage : neurological Consequences of highly pathogenic Fujian H5N1 strains.
abstract: The outbreak of H5N1 avian influenza strains infectious to human has dire neurological and pathological consequences. This led to the massive vaccination of host poultry, resulting in a Fujian-like variant (vFJ) resistant to immunization with two mutations at the furin-processing site of hemagglutinin: loss of the P2 Lys and P9 substitution of Gln to Leu within the cleavage site. We synthesized 14mer peptides mimicking the processing site of Fujian-like strains. We found that the peptide with the vFJ sequence is less cleaved as compared to the parent FJ-derived peptide by furin at either neutral or acidic pH values. We hypothesize that the double hemagglutinin mutations in vFJ may result in viruses with less processed hemagglutinin, thereby providing a mechanism for evading immune neutralization.
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pasquato
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive / Q000235:genetics; D001717:Birds; D019143:Evolution, Molecular; D045683:Furin / Q000737:chemistry* / Q000378:metabolism; D014644:Genetic Variation; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006493:Heparin / Q000737:chemistry; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000737:chemistry; D005585:Influenza in Birds / Q000235:genetics* / Q000517:prevention & control; D007251:Influenza, Human / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014611:Vaccination / Q000009:adverse effects; D014774:Virulence / Q000235:genetics
chemical_list: D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D010455:Peptides; D006493:Heparin; D045683:Furin