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Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity.
Cell. 2013 Jun 20; 153(7):1475-85.Cell

Abstract

Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to "quantitatively switch" its binding from avian to human glycan receptors. Here, we describe a structural framework that outlines a necessary set of H5 HA receptor-binding site (RBS) features required for the H5 HA to quantitatively switch its preference to human receptors. We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to a quantitative switch in receptor preference. We demonstrate that HAs from circulating clades require as few as a single base pair mutation to quantitatively switch their binding to human receptors. The mutations identified by this study can be used to monitor the emergence of strains having human-to-human transmission potential.

Authors+Show Affiliations

Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

23746829

Citation

Tharakaraman, Kannan, et al. "Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity." Cell, vol. 153, no. 7, 2013, pp. 1475-85.
Tharakaraman K, Raman R, Viswanathan K, et al. Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity. Cell. 2013;153(7):1475-85.
Tharakaraman, K., Raman, R., Viswanathan, K., Stebbins, N. W., Jayaraman, A., Krishnan, A., Sasisekharan, V., & Sasisekharan, R. (2013). Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity. Cell, 153(7), 1475-85. https://doi.org/10.1016/j.cell.2013.05.035
Tharakaraman K, et al. Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity. Cell. 2013 Jun 20;153(7):1475-85. PubMed PMID: 23746829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity. AU - Tharakaraman,Kannan, AU - Raman,Rahul, AU - Viswanathan,Karthik, AU - Stebbins,Nathan W, AU - Jayaraman,Akila, AU - Krishnan,Arvind, AU - Sasisekharan,V, AU - Sasisekharan,Ram, Y1 - 2013/06/06/ PY - 2013/04/05/received PY - 2013/05/09/revised PY - 2013/05/20/accepted PY - 2013/6/11/entrez PY - 2013/6/12/pubmed PY - 2013/8/31/medline SP - 1475 EP - 85 JF - Cell JO - Cell VL - 153 IS - 7 N2 - Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to "quantitatively switch" its binding from avian to human glycan receptors. Here, we describe a structural framework that outlines a necessary set of H5 HA receptor-binding site (RBS) features required for the H5 HA to quantitatively switch its preference to human receptors. We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to a quantitative switch in receptor preference. We demonstrate that HAs from circulating clades require as few as a single base pair mutation to quantitatively switch their binding to human receptors. The mutations identified by this study can be used to monitor the emergence of strains having human-to-human transmission potential. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/23746829/Structural_determinants_for_naturally_evolving_H5N1_hemagglutinin_to_switch_its_receptor_specificity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(13)00641-7 DB - PRIME DP - Unbound Medicine ER -