18-0616.pdf (2.35 MB)
Association of increased receptor-binding avidity of influenza A(H9N2) viruses with escape from antibody-based immunity and enhanced zoonotic potential
journal contributionposted on 2019-12-19, 18:07 authored by Joshua E Sealy, Tahir Yaqub, Thomas P Peacock, Pengxiang Chang, Burcu Ermetal, Anabel Clements, Jean-Remy Sadeyen, Arslan Mehboob, Holly Shelton, Juliet E Bryant, Rod S Daniels, John W McCauley, Munir Iqbal
We characterized 55 influenza A(H9N2) viruses isolated in Pakistan during 2014-2016 and found that the hemagglutinin gene is of the G1 lineage and that internal genes have differentiated into a variety of novel genotypes. Some isolates had up to 4-fold reduction in hemagglutination inhibition titers compared with older viruses. Viruses with hemagglutinin A180T/V substitutions conveyed this antigenic diversity and also caused up to 3,500-fold greater binding to avian-like and >20-fold greater binding to human-like sialic acid receptor analogs. This enhanced binding avidity led to reduced virus replication in primary and continuous cell culture. We confirmed that altered receptor-binding avidity of H9N2 viruses, including enhanced binding to human-like receptors, results in antigenic variation in avian influenza viruses. Consequently, current vaccine formulations might not induce adequate protective immunity in poultry, and emergence of isolates with marked avidity for human-like receptors increases the zoonotic risk.
Crick (Grant ID: 10030, Grant title: McCauley FC001030)
Pakistanantibody-based immunityenhanced zoonotic potentialinfluenzainfluenza A(H9N2) virusreceptor-binding avidityrespiratory infectionsvirus escapeviruseszoonosesAnimalsAntibodies, ViralAntibody AffinityAntigenic VariationBinding SitesErythrocytesHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A Virus, H9N2 SubtypeInfluenza in BirdsNeuraminidasePhylogenyPoultryPoultry DiseasesReceptors, Cell SurfaceZoonosesMcCauley FC001030WIC1108 Medical Microbiology1117 Public Health and Health Services1103 Clinical SciencesMicrobiology