10779/crick.11409672.v1
Joshua E Sealy
Joshua E
Sealy
Tahir Yaqub
Tahir
Yaqub
Thomas P Peacock
Thomas P
Peacock
Pengxiang Chang
Pengxiang
Chang
Burcu Ermetal
Burcu
Ermetal
Anabel Clements
Anabel
Clements
Jean-Remy Sadeyen
Jean-Remy
Sadeyen
Arslan Mehboob
Arslan
Mehboob
Holly Shelton
Holly
Shelton
Juliet E Bryant
Juliet E
Bryant
Rod S Daniels
Rod S
Daniels
John W McCauley
John W
McCauley
Munir Iqbal
Munir
Iqbal
Association of increased receptor-binding avidity of influenza A(H9N2) viruses with escape from antibody-based immunity and enhanced zoonotic potential
The Francis Crick Institute
2019
Pakistan
antibody-based immunity
enhanced zoonotic potential
influenza
influenza A(H9N2) virus
receptor-binding avidity
respiratory infections
virus escape
viruses
zoonoses
Animals
Antibodies, Viral
Antibody Affinity
Antigenic Variation
Binding Sites
Erythrocytes
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Influenza A Virus, H9N2 Subtype
Influenza in Birds
Neuraminidase
Phylogeny
Poultry
Poultry Diseases
Receptors, Cell Surface
Zoonoses
McCauley FC001030
WIC
1108 Medical Microbiology
1117 Public Health and Health Services
1103 Clinical Sciences
Microbiology
2019-12-19 18:07:47
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Association_of_increased_receptor-binding_avidity_of_influenza_A_H9N2_viruses_with_escape_from_antibody-based_immunity_and_enhanced_zoonotic_potential/11409672
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.