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Analysis of the Contrasting Pathogenicities Induced by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses
[Image: see text] In 2009, the D222G mutation in the hemagglutinin (HA) glycoprotein of pandemic H1N1 influenza A virus was found to correlate with fatal and severe human infections. Previous static structural analysis suggested that, unlike the H1N1 viruses prevalent in 1918, the mutation did not c...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547735/ https://www.ncbi.nlm.nih.gov/pubmed/26321885 http://dx.doi.org/10.1021/ct5010565 |
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author | Shang, Cheng Whittleston, Chris S. Sutherland-Cash, Kyle H. Wales, David J. |
author_facet | Shang, Cheng Whittleston, Chris S. Sutherland-Cash, Kyle H. Wales, David J. |
author_sort | Shang, Cheng |
collection | PubMed |
description | [Image: see text] In 2009, the D222G mutation in the hemagglutinin (HA) glycoprotein of pandemic H1N1 influenza A virus was found to correlate with fatal and severe human infections. Previous static structural analysis suggested that, unlike the H1N1 viruses prevalent in 1918, the mutation did not compromise binding to human α2,6-linked glycan receptors, allowing it to transmit efficiently. Here we investigate the interconversion mechanism between two predicted binding modes in both 2009 and 1918 HAs, introducing a highly parallel intermediate network search scheme to construct kinetically relevant pathways efficiently. Accumulated mutations at positions 183 and 224 that alter the size of the binding pocket are identified with the fitness of the 2009 pandemic virus carrying the D222G mutation. This result suggests that the pandemic H1N1 viruses could gain binding affinity to the α2,3-linked glycan receptors in the lungs, usually associated with highly pathogenic avian influenza, without compromising viability. |
format | Online Article Text |
id | pubmed-4547735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-45477352015-08-26 Analysis of the Contrasting Pathogenicities Induced by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses Shang, Cheng Whittleston, Chris S. Sutherland-Cash, Kyle H. Wales, David J. J Chem Theory Comput [Image: see text] In 2009, the D222G mutation in the hemagglutinin (HA) glycoprotein of pandemic H1N1 influenza A virus was found to correlate with fatal and severe human infections. Previous static structural analysis suggested that, unlike the H1N1 viruses prevalent in 1918, the mutation did not compromise binding to human α2,6-linked glycan receptors, allowing it to transmit efficiently. Here we investigate the interconversion mechanism between two predicted binding modes in both 2009 and 1918 HAs, introducing a highly parallel intermediate network search scheme to construct kinetically relevant pathways efficiently. Accumulated mutations at positions 183 and 224 that alter the size of the binding pocket are identified with the fitness of the 2009 pandemic virus carrying the D222G mutation. This result suggests that the pandemic H1N1 viruses could gain binding affinity to the α2,3-linked glycan receptors in the lungs, usually associated with highly pathogenic avian influenza, without compromising viability. American Chemical Society 2015-03-24 2015-05-12 /pmc/articles/PMC4547735/ /pubmed/26321885 http://dx.doi.org/10.1021/ct5010565 Text en Copyright © 2015 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Shang, Cheng Whittleston, Chris S. Sutherland-Cash, Kyle H. Wales, David J. Analysis of the Contrasting Pathogenicities Induced by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses |
title | Analysis
of the Contrasting Pathogenicities Induced
by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses |
title_full | Analysis
of the Contrasting Pathogenicities Induced
by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses |
title_fullStr | Analysis
of the Contrasting Pathogenicities Induced
by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses |
title_full_unstemmed | Analysis
of the Contrasting Pathogenicities Induced
by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses |
title_short | Analysis
of the Contrasting Pathogenicities Induced
by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses |
title_sort | analysis
of the contrasting pathogenicities induced
by the d222g mutation in 1918 and 2009 pandemic influenza a viruses |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547735/ https://www.ncbi.nlm.nih.gov/pubmed/26321885 http://dx.doi.org/10.1021/ct5010565 |
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