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Quantitative characterization of glycan-receptor binding of H9N2 influenza A virus hemagglutinin.
PLoS One. 2013; 8(4):e59550.Plos

Abstract

Avian influenza subtypes such as H5, H7 and H9 are yet to adapt to the human host so as to establish airborne transmission between humans. However, lab-generated reassorted viruses possessing hemagglutinin (HA) and neuraminidase (NA) genes from an avian H9 isolate and other genes from a human-adapted (H3 or H1) subtype acquired two amino acid changes in HA and a single amino acid change in NA that confer respiratory droplet transmission in ferrets. We previously demonstrated for human-adapted H1, H2 and H3 subtypes that quantitative binding affinity of their HA to α2→6 sialylated glycan receptors correlates with respiratory droplet transmissibility of the virus in ferrets. Such a relationship remains to be established for H9 HA. In this study, we performed a quantitative biochemical characterization of glycan receptor binding properties of wild-type and mutant forms of representative H9 HAs that were previously used in context of reassorted viruses in ferret transmission studies. We demonstrate here that distinct molecular interactions in the glycan receptor-binding site of different H9 HAs affect the glycan-binding specificity and affinity. Further we show that α2→6 glycan receptor-binding affinity of a mutant H9 HA carrying Thr-189→Ala amino acid change correlates with the respiratory droplet transmission in ferrets conferred by this change. Our findings contribute to a framework for monitoring the evolution of H9 HA by understanding effects of molecular changes in HA on glycan receptor-binding properties.

Authors+Show Affiliations

Harvard-MIT Division of Health Sciences and Technology, Koch Institute for Integrative Cancer Research, Singapore-MIT Alliance for Research and Technology, Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23626667

Citation

Srinivasan, Karunya, et al. "Quantitative Characterization of Glycan-receptor Binding of H9N2 Influenza a Virus Hemagglutinin." PloS One, vol. 8, no. 4, 2013, pp. e59550.
Srinivasan K, Raman R, Jayaraman A, et al. Quantitative characterization of glycan-receptor binding of H9N2 influenza A virus hemagglutinin. PLoS ONE. 2013;8(4):e59550.
Srinivasan, K., Raman, R., Jayaraman, A., Viswanathan, K., & Sasisekharan, R. (2013). Quantitative characterization of glycan-receptor binding of H9N2 influenza A virus hemagglutinin. PloS One, 8(4), e59550. https://doi.org/10.1371/journal.pone.0059550
Srinivasan K, et al. Quantitative Characterization of Glycan-receptor Binding of H9N2 Influenza a Virus Hemagglutinin. PLoS ONE. 2013;8(4):e59550. PubMed PMID: 23626667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantitative characterization of glycan-receptor binding of H9N2 influenza A virus hemagglutinin. AU - Srinivasan,Karunya, AU - Raman,Rahul, AU - Jayaraman,Akila, AU - Viswanathan,Karthik, AU - Sasisekharan,Ram, Y1 - 2013/04/23/ PY - 2012/05/01/received PY - 2013/02/19/accepted PY - 2013/4/30/entrez PY - 2013/4/30/pubmed PY - 2013/12/16/medline SP - e59550 EP - e59550 JF - PloS one JO - PLoS ONE VL - 8 IS - 4 N2 - Avian influenza subtypes such as H5, H7 and H9 are yet to adapt to the human host so as to establish airborne transmission between humans. However, lab-generated reassorted viruses possessing hemagglutinin (HA) and neuraminidase (NA) genes from an avian H9 isolate and other genes from a human-adapted (H3 or H1) subtype acquired two amino acid changes in HA and a single amino acid change in NA that confer respiratory droplet transmission in ferrets. We previously demonstrated for human-adapted H1, H2 and H3 subtypes that quantitative binding affinity of their HA to α2→6 sialylated glycan receptors correlates with respiratory droplet transmissibility of the virus in ferrets. Such a relationship remains to be established for H9 HA. In this study, we performed a quantitative biochemical characterization of glycan receptor binding properties of wild-type and mutant forms of representative H9 HAs that were previously used in context of reassorted viruses in ferret transmission studies. We demonstrate here that distinct molecular interactions in the glycan receptor-binding site of different H9 HAs affect the glycan-binding specificity and affinity. Further we show that α2→6 glycan receptor-binding affinity of a mutant H9 HA carrying Thr-189→Ala amino acid change correlates with the respiratory droplet transmission in ferrets conferred by this change. Our findings contribute to a framework for monitoring the evolution of H9 HA by understanding effects of molecular changes in HA on glycan receptor-binding properties. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23626667/Quantitative_characterization_of_glycan_receptor_binding_of_H9N2_influenza_A_virus_hemagglutinin_ L2 - http://dx.plos.org/10.1371/journal.pone.0059550 DB - PRIME DP - Unbound Medicine ER -