Recent studies have identified several mutations in the hemagglutinin (HA) protein that allow the highly pathogenic avian H5N1 influenza A virus to transmit between mammals by airborne route. Here, we determined the complex structures of wild-type and mutant HAs derived from an Indonesia H5N1 virus bound to either avian or human receptor sialic acid analogs. A cis/trans conformational change in the glycosidic linkage of the receptor analog was observed, which explains how the H5N1 virus alters its receptor-binding preference. Furthermore, the mutant HA possessed low affinities for both avian and human receptors. Our findings provide a structural and biophysical basis for the H5N1 adaptation to acquire human, but maintain avian, receptor-binding properties.
Mutations in the H5N1 hemagglutinin altered receptor-binding conformation and affinity, supporting molecular adaptation for human-type receptor recognition associated with airborne transmissibility among mammals.
Several mutations in the hemagglutinin (HA) protein allow the highly pathogenic avian H5N1 influenza A virus to transmit between mammals by airborne route. Structural analysis showed changes in HA receptor-binding preference between avian and human sialic acid analogs, explaining H5N1 adaptation to acquire human while maintaining avian receptor-binding properties.
Genes or proteins
hemagglutinin (HA)
Receptors
avian receptor sialic acid; human receptor sialic acid
Mechanism types
receptor_binding; host_range; tropism
Receptor Usage1 records
Receptor UsageExtraction confidence 0.95
Key finding
Structural analysis showed that mutant H5N1 influenza hemagglutinin binds both avian- and human-type sialic acid receptors, with altered binding preference due to a conformational change in the receptor analog.
We determined the complex structures of wild-type and mutant HAs derived from an Indonesia H5N1 virus bound to either avian or human receptor sialic acid analogs. A cis/trans conformational change in the glycosidic linkage of the receptor analog was observed, which explains how the H5N1 virus alters its receptor-binding preference.
