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Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses

BACKGROUND: The 1918 H1N1 virus was a highly virulent strain that killed 20–50 million people. The cause of its virulence remains poorly understood. METHODS: Intrinsic disorder predictor PONDR(® )VLXT was used to compare various influenza subtypes and strains. Three-dimensional models using data fro...

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Autores principales: Goh, Gerard Kian-Meng, Dunker, A Keith, Uversky, Vladimir N
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701943/
https://www.ncbi.nlm.nih.gov/pubmed/19493338
http://dx.doi.org/10.1186/1743-422X-6-69
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author Goh, Gerard Kian-Meng
Dunker, A Keith
Uversky, Vladimir N
author_facet Goh, Gerard Kian-Meng
Dunker, A Keith
Uversky, Vladimir N
author_sort Goh, Gerard Kian-Meng
collection PubMed
description BACKGROUND: The 1918 H1N1 virus was a highly virulent strain that killed 20–50 million people. The cause of its virulence remains poorly understood. METHODS: Intrinsic disorder predictor PONDR(® )VLXT was used to compare various influenza subtypes and strains. Three-dimensional models using data from X-ray crystallographic studies annotated with disorder prediction were used to characterize the proteins. RESULTS: The protein of interest is hemagglutin (HA), which is a surface glycoprotein that plays a vital role in viral entry. Distinct differences between HA proteins of the virulent and non-virulent strains are seen, especially in the region near residues 68–79 of the HA(2). This region represents the tip of the stalk that is in contact with the receptor chain, HA(1), and therefore likely to provide the greatest effect on the motions of the exposed portion of HA. Comparison of this region between virulent strains (1918 H1N1 and H5N1) and less virulent ones (H3N2 and 1930 H1N1) reveals that predicted disorder can be seen at this region among the more virulent strains and subtypes but is remarkably absent among the distinctly less virulent ones. CONCLUSION: The motions created by disorder at crucial regions are likely to impair recognition by immunological molecules and increase the virulence of both the H5N1 and the 1918 H1N1 viruses. The results help explain many puzzling features of the H5N1 and the 1918 H1N1 viruses. Summarizing, HA (and especially its intrinsically disordered regions) can serve as a predictor of the influenza A virulence, even though there may be other proteins that contribute to or exacerbate the virulence.
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spelling pubmed-27019432009-06-26 Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses Goh, Gerard Kian-Meng Dunker, A Keith Uversky, Vladimir N Virol J Research BACKGROUND: The 1918 H1N1 virus was a highly virulent strain that killed 20–50 million people. The cause of its virulence remains poorly understood. METHODS: Intrinsic disorder predictor PONDR(® )VLXT was used to compare various influenza subtypes and strains. Three-dimensional models using data from X-ray crystallographic studies annotated with disorder prediction were used to characterize the proteins. RESULTS: The protein of interest is hemagglutin (HA), which is a surface glycoprotein that plays a vital role in viral entry. Distinct differences between HA proteins of the virulent and non-virulent strains are seen, especially in the region near residues 68–79 of the HA(2). This region represents the tip of the stalk that is in contact with the receptor chain, HA(1), and therefore likely to provide the greatest effect on the motions of the exposed portion of HA. Comparison of this region between virulent strains (1918 H1N1 and H5N1) and less virulent ones (H3N2 and 1930 H1N1) reveals that predicted disorder can be seen at this region among the more virulent strains and subtypes but is remarkably absent among the distinctly less virulent ones. CONCLUSION: The motions created by disorder at crucial regions are likely to impair recognition by immunological molecules and increase the virulence of both the H5N1 and the 1918 H1N1 viruses. The results help explain many puzzling features of the H5N1 and the 1918 H1N1 viruses. Summarizing, HA (and especially its intrinsically disordered regions) can serve as a predictor of the influenza A virulence, even though there may be other proteins that contribute to or exacerbate the virulence. BioMed Central 2009-06-03 /pmc/articles/PMC2701943/ /pubmed/19493338 http://dx.doi.org/10.1186/1743-422X-6-69 Text en Copyright © 2009 Goh et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Goh, Gerard Kian-Meng
Dunker, A Keith
Uversky, Vladimir N
Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses
title Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses
title_full Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses
title_fullStr Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses
title_full_unstemmed Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses
title_short Protein intrinsic disorder and influenza virulence: the 1918 H1N1 and H5N1 viruses
title_sort protein intrinsic disorder and influenza virulence: the 1918 h1n1 and h5n1 viruses
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701943/
https://www.ncbi.nlm.nih.gov/pubmed/19493338
http://dx.doi.org/10.1186/1743-422X-6-69
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