Journal ArticleDOI
Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors
Shinya Yamada,Yasuo Suzuki,Takashi Suzuki,Mai Q. Le,Chairul A. Nidom,Yuko Sakai-Tagawa,Yukiko Muramoto,Mutsumi Ito,Maki Kiso,Taisuke Horimoto,Kyoko Shinya,Toshihiko Sawada,Makoto Kiso,Taiichi Usui,Takeomi Murata,Yipu Lin,Alan Hay,Lesley F. Haire,D.J. Stevens,Rupert J. Russell,Rupert J. Russell,Steven J. Gamblin,John J. Skehel,Yoshihiro Kawaoka +23 more
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TLDR
It is shown that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptor exclusively.Abstract:
H5N1 influenza A viruses have spread to numerous countries in Asia, Europe and Africa, infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects. Human and avian influenza A viruses differ in their recognition of host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-alpha2,6-galactose (SAalpha2,6Gal), whereas the latter prefer those ending in SAalpha2,3Gal (refs 3-6). A conversion from SAalpha2,3Gal to SAalpha2,6Gal recognition is thought to be one of the changes that must occur before avian influenza viruses can replicate efficiently in humans and acquire the potential to cause a pandemic. By identifying mutations in the receptor-binding haemagglutinin (HA) molecule that would enable avian H5N1 viruses to recognize human-type host cell receptors, it may be possible to predict (and thus to increase preparedness for) the emergence of pandemic viruses. Here we show that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptors exclusively. Mutations at positions 182 and 192 independently convert the HAs of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. Analysis of the crystal structure of the HA from an H5N1 virus used in our genetic experiments shows that the locations of these amino acids in the HA molecule are compatible with an effect on receptor binding. The amino acid changes that we identify might serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.read more
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Journal ArticleDOI
Emergence and pandemic potential of swine-origin H1N1 influenza virus.
TL;DR: Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.
Journal ArticleDOI
Airborne transmission of influenza A/H5N1 virus between ferrets
Sander Herfst,Eefje J. A. Schrauwen,Martin Linster,Salin Chutinimitkul,Emmie de Wit,Vincent J. Munster,Erin M. Sorrell,Theo M. Bestebroer,David F. Burke,Derek J. Smith,Derek J. Smith,Derek J. Smith,Guus F. Rimmelzwaan,Albert D. M. E. Osterhaus,Ron A. M. Fouchier +14 more
TL;DR: Avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.
Journal ArticleDOI
Antibody Recognition of a Highly Conserved Influenza Virus Epitope
Damian C. Ekiert,Gira Bhabha,Marc-André Elsliger,Robert H. E. Friesen,Mandy Jongeneelen,Mark Throsby,Jaap Goudsmit,Ian A. Wilson +7 more
TL;DR: TheCR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.
Journal ArticleDOI
Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets
Masaki Imai,Tokiko Watanabe,Masato Hatta,Subash C. Das,Makoto Ozawa,Makoto Ozawa,Kyoko Shinya,Gongxun Zhong,Anthony Hanson,Hiroaki Katsura,Shinji Watanabe,Chengjun Li,Eiryo Kawakami,Shinya Yamada,Maki Kiso,Yasuo Suzuki,Eileen A. Maher,Gabriele Neumann,Yoshihiro Kawaoka +18 more
TL;DR: Results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolate, which will inform the development, production and distribution of effective countermeasures.
Journal ArticleDOI
Structural and Functional Bases for Broad-Spectrum Neutralization of Avian and Human Influenza A Viruses
Jianhua Sui,William C. Hwang,Sandra Elizabeth Pérez,Ge Wei,Daniel Aird,Li-Mei Chen,Eugenio Santelli,Boguslaw Stec,Greg Cadwell,Maryam Ali,Hongquan Wan,Akikazu Murakami,Anuradha Yammanuru,Thomas Han,Nancy J. Cox,Laurie A. Bankston,Ruben O. Donis,Robert C. Liddington,Wayne A. Marasco +18 more
TL;DR: The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion, and suggests that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
References
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Journal ArticleDOI
The CCP4 suite: programs for protein crystallography
TL;DR: The CCP4 (Collaborative Computational Project, number 4) program suite is a collection of programs and associated data and subroutine libraries which can be used for macromolecular structure determination by X-ray crystallography.
Journal ArticleDOI
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Axel T. Brunger,Axel T. Brunger,Paul D. Adams,G M Clore,W. L. DeLano,Piet Gros,R.W. Grosse-Kunstleve,R.W. Grosse-Kunstleve,Jiansheng Jiang,J. Kuszewski,Michael Nilges,Navraj S. Pannu,Randy J. Read,Luke M. Rice,Thomas Simonson,Gregory L. Warren +15 more
TL;DR: The Crystallography & NMR System (CNS) as mentioned in this paper is a software suite for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy.
Journal ArticleDOI
Improved methods for building protein models in electron density maps and the location of errors in these models.
TL;DR: In this paper, the authors describe strategies and tools that help to alleviate this problem and simplify the model-building process, quantify the goodness of fit of the model on a per-residue basis and locate possible errors in peptide and side-chain conformations.
Journal ArticleDOI
Generation of influenza A viruses entirely from cloned cDNAs
Gabriele Neumann,Tokiko Watanabe,Hiroshi Ito,Shinji Watanabe,Hideo Goto,Peng Gao,Mark A. Hughes,Daniel R. Perez,Ruben O. Donis,Erich Hoffmann,Gerd Hobom,Yoshihiro Kawaoka +11 more
TL;DR: A new reverse-genetics system that allows one to efficiently generate influenza A viruses entirely from cloned cDNAs is described, which should be useful in viral mutagenesis studies and in the production of vaccines and gene therapy vectors.
Journal ArticleDOI
Avian flu: influenza virus receptors in the human airway.
TL;DR: An anatomical difference in the distribution in the human airway of the different binding molecules preferred by the avian and human influenza viruses is demonstrated to provide a rational explanation for why H5N1 viruses at present rarely infect and spread between humans although they can replicate efficiently in the lungs.
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