tetano
Editor, Senior Moderator
Virology. 2013 Sep 17. pii: S0042-6822(13)00481-9. doi: 10.1016/j.virol.2013.08.010. [Epub ahead of print]
Changes in the hemagglutinin of H5N1 viruses during human infection - Influence on receptor binding.
Crusat M, Liu J, Palma AS, Childs RA, Liu Y, Wharton SA, Lin YP, Coombs PJ, Martin SR, Matrosovich M, Chen Z, Stevens DJ, Hien VM, Thanh TT, Nhu LN, Nguyet LA, Ha DQ, van Doorn HR, Hien TT, Conradt HS, Kiso M, Gamblin SJ, Chai W, Skehel JJ, Hay AJ, Farrar J, de Jong MD, Feizi T.
Source
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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.
? 2013 The Authros. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Biolayer interferometry, Carbohydrate microarray, H5N1 influenza infection, Hemagglutination assays, Hemagglutinin, Hemagglutinin X-ray crystal structure, Pyrosequencing, Receptor binding, Receptor specificity, Synthetic sialylglycopolymers
PMID:
24050651
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24050651
Changes in the hemagglutinin of H5N1 viruses during human infection - Influence on receptor binding.
Crusat M, Liu J, Palma AS, Childs RA, Liu Y, Wharton SA, Lin YP, Coombs PJ, Martin SR, Matrosovich M, Chen Z, Stevens DJ, Hien VM, Thanh TT, Nhu LN, Nguyet LA, Ha DQ, van Doorn HR, Hien TT, Conradt HS, Kiso M, Gamblin SJ, Chai W, Skehel JJ, Hay AJ, Farrar J, de Jong MD, Feizi T.
Source
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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.
? 2013 The Authros. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Biolayer interferometry, Carbohydrate microarray, H5N1 influenza infection, Hemagglutination assays, Hemagglutinin, Hemagglutinin X-ray crystal structure, Pyrosequencing, Receptor binding, Receptor specificity, Synthetic sialylglycopolymers
PMID:
24050651
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24050651