Hemagglutinin receptor specificity and structural analyses of respiratory droplet-transmissible H5N1 viruses.
Robert P de Vries1
Xueyong Zhu
Ryan McBride
Alan Rigter
Anthony Hanson
Gongxun Zhong
Masato Hatta
Rui Xu
Wenli Yu
Yoshihiro Kawaoka
Cornelis A M de Haan
Ian A Wilson
James C Paulson
Affiliations1 institutions
Departments of Cell and Molecular Biology and Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA.
Two ferret-adapted H5N1 viruses capable of respiratory droplet transmission have been reported with mutations in the hemagglutinin receptor-binding site and stalk domains. Glycan microarray analysis reveals that both viruses exhibit a strong shift toward binding to "human-type" α2-6 sialosides but with notable differences in fine specificity. Crystal structure analysis further shows that the stalk mutation causes no obvious perturbation of the receptor-binding pocket, consistent with its impact on hemagglutinin stability without affecting receptor specificity.
HemagglutininsHumansInfluenza A Virus, H5N1 Subtype
Structured evidence records
Evidence records
3 total
Host Range Experiment1 records
Host Range ExperimentExtraction confidence 0.85
Key finding
Ferret-adapted H5N1 viruses showed altered receptor binding toward human-type α2-6 sialosides, indicating experimental evidence of mammalian transmissibility and host range adaptation.
Two ferret-adapted H5N1 viruses capable of respiratory droplet transmission have been reported with mutations in the hemagglutinin receptor-binding site and stalk domains. Glycan microarray analysis reveals that both viruses exhibit a strong shift toward binding to 'human-type' α2-6 sialosides.
Method
ferret adaptation; glycan microarray analysis
Experimental system
in vivo animal experiment
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.90
Key finding
Mutations in the hemagglutinin receptor-binding site and stalk of ferret-adapted H5N1 viruses shift receptor binding toward human-type α2-6 sialosides, indicating adaptation for mammalian transmission.
Two ferret-adapted H5N1 viruses capable of respiratory droplet transmission have been reported with mutations in the hemagglutinin receptor-binding site and stalk domains. Glycan microarray analysis reveals that both viruses exhibit a strong shift toward binding to 'human-type' α2-6 sialosides but with notable differences in fine specificity.
Genes or proteins
hemagglutinin
Receptors
α2-6 sialosides
Mechanism types
receptor_binding; host_range_adaptation
Receptor Usage1 records
Receptor UsageExtraction confidence 0.95
Key finding
Ferret-adapted H5N1 viruses show a shift in hemagglutinin receptor-binding preference toward human-type α2-6 sialoside receptors, indicating altered receptor specificity associated with airborne transmissibility.
Glycan microarray analysis reveals that both ferret-adapted H5N1 viruses exhibit a strong shift toward binding to 'human-type' α2-6 sialosides but with notable differences in fine specificity.
2012. The role of receptor binding specificity in interspecies transmission of influenza viruses. Curr. Opin. Virol. 2:160–167. 10.1016/j.coviro.2012.03.003
2012. Recognition of sialylated poly-N-acetyllactosamine chains on N- and O-linked glycans by human and avian influenza a virus hemagglutinins. Angew. Chem. Int. Ed. Engl. 51:4860–4863. 10.1002/anie.201200596
