The H5N1 influenza variant Fujian-like hemagglutinin selected following vaccination exhibits a compromised furin cleavage : neurological Consequences of highly pathogenic Fujian H5N1 strains.
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.
Pasquato
Antonella
A
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
Seidah
Nabil G
NG
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
D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D010455:Peptides; D006493:Heparin; D045683:Furin