Hemagglutinin Receptor Binding of a Human Isolate of Influenza A(H10N8) Virus - Volume 21, Number 7—July 2015 - Emerging Infectious Disease journal - CDC

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Hemagglutinin Receptor Binding of a Human Isolate of Influenza A(H10N8) Virus - Volume 21, Number 7—July 2015 - Emerging Infectious Disease journal - CDC

Volume 21, Number 7—July 2015

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Hemagglutinin Receptor Binding of a Human Isolate of Influenza A(H10N8) Virus

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• The Study
• Conclusions
• Suggested Citation

Figures

• Figure 1
• Figure 2
• Figure 3

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Irene Ramos , Mena Mansour, Teddy J. Wohlbold, Megan E. Ermler, Ariana Hirsh, Jonathan A. Runstadler, Ana Fernandez-Sesma, and Florian Krammer 

Author affiliations: Icahn School of Medicine at Mount Sinai, New York, New York, USA (I. Ramos, M. Mansour, T.J. Wohlbold, M.E. Ermler, A. Hirsh, A. Fernandez-Sesma, F. Krammer); Massachusetts Institute of Technology, Cambridge Massachusetts, USA (J.A. Runstadler)

Suggested citation for this article

Abstract

Three cases of influenza A(H10N8) virus infection in humans have been reported; 2 of these infected persons died. Characterization of the receptor binding pattern of H10 hemagglutinin from avian and human isolates showed that both interact weakly with human-like receptors and maintain strong affinity for avian-like receptors.

Human infections with avian influenza A(H10N8) virus were reported in China during the 2013–14 winter influenza season. The first patient, a 73-year old woman, became ill in November 2013 a few days after visiting a live poultry market in Jiangxi Province (1). Two additional patients, a 55-year-old woman and a 75-year-old man, were admitted to hospitals in the same province in January 2014 (2). Severe pneumonia and subsequent acute respiratory distress syndrome developed in all 3 patients; 2 of the patients died, 5 and 6 days after admission (2).

Epithelial cells of the human upper respiratory tract contain mostly α2,6-linked sialic acids (SAα2,6) and low levels of α2,3-linked sialic acids (SAα2,3) (3). Hemagglutinin (HA) of avian influenza virus strains shows preferential binding to SAα2,3 receptors, which partially accounts for the reduced ability of avian influenza strains to establish infections in humans (3). Interaction with SAα2,6 receptors is one of the requirements for efficient replication in the human upper respiratory tract. In addition, reduced binding to SAα2,3 facilitates respiratory droplet-based transmission in ferrets (4). Therefore, emerging avian influenza viruses with increased binding to SAα2,6 and reduced binding to SAα2,3 pose a major pandemic threat, and active research and surveillance to detect animal viruses with modified receptor binding are warranted.

Dr. Ramos is an assistant professor in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY. Her main research interests focus on receptors for influenza viruses and innate immunity to these viruses.

Acknowledgments

We thank CFG for providing reagents. Some of the data will be published on the CFG website (http://www.functionalglycomics.org/). We also thank the Flow Cytometry Shared Facility and the Microscopy Core Facility at Icahn School of Medicine at Mount Sinai for assistance, the Icahn School of Medicine Institutional Biorepository for providing human tissue sections, John Steel and Randy A. Albrecht for providing recombinant influenza viruses, and GISAID for making H10N7 and H10N8 subtype virus sequencing data publicly available.

This study was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (Center for Research on Influenza Pathogenesis, contract HHSN272201400008C to J.A.R., F.K., and A.F.-S.) as part of the Centers for Excellence for Influenza Research and Surveillance Network. I.R. was partially supported by National Institutes of Health training grant T32 AI788926.

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Figures

• Figure 1. Receptor binding specificity of hemagglutinin of influenza A(H10N8) virus H10-JD346. A) Binding of recombinant hemagglutinins to glycans in a solid-phase binding assay. Results are means ± SEM of triplicate...
• Figure 2. Interaction of hemagglutinin (HA) of H3-P99 (panels B and E) and H10-JD346 (panels C, F, and G) isolates of influenza A(H10N8) viruses with human trachea. Sections from 2 persons...
• Figure 3. Replication of influenza A(H10N8) H10-JD346 virus in human epithelial cells. A549 cells (a human lung epithelial adenocarcinoma cell line) were infected at a multiplicity of infection of 0.1 with...

Table

• Table. Alignment of residues involved receptor binding of hemagglutinin of influenza A viruses

Suggested citation for this article: Ramos I, Mansour M, Wohlbold TJ, Ermler ME, Hirsh A, Runstadler JA, et al. Hemagglutinin receptor binding of a human isolate of influenza A(H10N8) virus. Emerg Infect Dis. 2015 Jul [date cited]. http://dx.doi.org/10.3201/eid2107.141755

DOI: 10.3201/eid2107.141755