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Changes in the hemagglutinin of H5N1 viruses during human infection – Influence on receptor binding

DOI: 10.1016/j.virol.2013.08.010 DOI Help
PMID: 24050651 PMID Help

Authors: Martin Crusat (Hospital for Tropical Diseases, Vietnam) , Junfeng Liu (MRC National Institute for Medical Research) , Angelina Sa Palma (Imperial College London) , Robert A. Childs (Imperial College London) , Yan Liu (Imperial College London) , Stephen A. Wharton (MRC National Institute for Medical Research) , Yi Pu Lin (MRC National Institute for Medical Research) , Peter J. Coombs (MRC National Institute for Medical Research) , Stephen R. Martin (MRC National Institute for Medical Research) , Mikhail Matrosovich (Philipps University) , Zi Chen (MRC National Institute for Medical Research) , David J. Stevens (MRC National Institute for Medical Research) , Vo Minh Hien (Hospital for Tropical Diseases, Vietnam) , Tran Tan Thanh (Hospital for Tropical Diseases, Vietnam) , Le Nguyen Truc Nhu (Hospital for Tropical Diseases, Vietnam) , Lam Anh Nguyet (Hospital for Tropical Diseases, Vietnam) , Do Quang Ha (Hospital for Tropical Diseases, Vietnam) , H Rogier Van Doorn (Hospital for Tropical Diseases, Vietnam) , Tran Tinh Hien (Hospital for Tropical Diseases, Vietnam) , Harald S. Conradt (GlycoThera GmbH) , Makoto Kiso (Gifu University) , Steven Gamblin (National Institute for Medical Research, Medical Research Council) , Wengang Chai (Imperial College London) , John J. Skehel (MRC National Institute for Medical Research) , Alan J. Hay (MRC National Institute for Medical Research) , Jeremy Farrar (Hospital for Tropical Diseases, Vietnam) , Menno D. De Jong (Hospital for Tropical Diseases, Vietnam) , Ten Feizi (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Virology , VOL 447 (1) , PAGES 326 - 337

State: Published (Approved)
Published: December 2013

Abstract: As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process.

Journal Keywords: Crystallography; X-Ray; Hemagglutinin; Influenza; Humans; Influenza; H5N1; Influenza; Influenza; Human; Mutant; Mutation; Missense; Poultry; Protein; RNA; Viral; Receptors; Virus; Sequence; DNA; Virus Attachment

Diamond Keywords: Viruses; Avian Flu

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I03-Macromolecular Crystallography

Added On: 19/02/2016 12:29

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)