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The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus

BACKGROUND: The influenza A virus genome is composed of eight single-stranded RNA segments of negative polarity. Although the hemagglutinin and neuraminidase genes are known to play a key role in host adaptation, the polymerase genes (which encode the polymerase segments PB2, PB1, PA) and the nucleo...

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Autores principales: Brower-Sinning, Rachel, Carter, Donald M, Crevar, Corey J, Ghedin, Elodie, Ross, Ted M, Benos, Panayiotis V
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688270/
https://www.ncbi.nlm.nih.gov/pubmed/19216739
http://dx.doi.org/10.1186/gb-2009-10-2-r18
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author Brower-Sinning, Rachel
Carter, Donald M
Crevar, Corey J
Ghedin, Elodie
Ross, Ted M
Benos, Panayiotis V
author_facet Brower-Sinning, Rachel
Carter, Donald M
Crevar, Corey J
Ghedin, Elodie
Ross, Ted M
Benos, Panayiotis V
author_sort Brower-Sinning, Rachel
collection PubMed
description BACKGROUND: The influenza A virus genome is composed of eight single-stranded RNA segments of negative polarity. Although the hemagglutinin and neuraminidase genes are known to play a key role in host adaptation, the polymerase genes (which encode the polymerase segments PB2, PB1, PA) and the nucleoprotein gene are also important for the efficient propagation of the virus in the host and for its adaptation to new hosts. Current efforts to understand the host-specificity of the virus have largely focused on the amino acid differences between avian and human isolates. RESULTS: Here we show that the folding free energy of the RNA segments may play an equally important role in the evolution and host adaptation of the influenza virus. Folding free energy may affect the stability of the viral RNA and influence the rate of viral protein translation. We found that there is a clear distinction between the avian and human folding free energy distributions for the polymerase and the nucleoprotein genes, with human viruses having substantially higher folding free energy values. This difference is independent of the amino acid composition and the codon bias. Furthermore, the folding free energy values of the commonly circulating human viruses tend to shift towards higher values over the years, after they entered the human population. Finally, our results indicate that the temperature in which the cells grow affects infection efficiency. CONCLUSIONS: Our data suggest for the first time that RNA structure stability may play an important role in the emergence and host shift of influenza A virus. The fact that cell temperature affects virus propagation in mammalian cells could help identify those avian strains that pose a higher threat to humans.
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spelling pubmed-26882702009-05-29 The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus Brower-Sinning, Rachel Carter, Donald M Crevar, Corey J Ghedin, Elodie Ross, Ted M Benos, Panayiotis V Genome Biol Research BACKGROUND: The influenza A virus genome is composed of eight single-stranded RNA segments of negative polarity. Although the hemagglutinin and neuraminidase genes are known to play a key role in host adaptation, the polymerase genes (which encode the polymerase segments PB2, PB1, PA) and the nucleoprotein gene are also important for the efficient propagation of the virus in the host and for its adaptation to new hosts. Current efforts to understand the host-specificity of the virus have largely focused on the amino acid differences between avian and human isolates. RESULTS: Here we show that the folding free energy of the RNA segments may play an equally important role in the evolution and host adaptation of the influenza virus. Folding free energy may affect the stability of the viral RNA and influence the rate of viral protein translation. We found that there is a clear distinction between the avian and human folding free energy distributions for the polymerase and the nucleoprotein genes, with human viruses having substantially higher folding free energy values. This difference is independent of the amino acid composition and the codon bias. Furthermore, the folding free energy values of the commonly circulating human viruses tend to shift towards higher values over the years, after they entered the human population. Finally, our results indicate that the temperature in which the cells grow affects infection efficiency. CONCLUSIONS: Our data suggest for the first time that RNA structure stability may play an important role in the emergence and host shift of influenza A virus. The fact that cell temperature affects virus propagation in mammalian cells could help identify those avian strains that pose a higher threat to humans. BioMed Central 2009 2009-02-12 /pmc/articles/PMC2688270/ /pubmed/19216739 http://dx.doi.org/10.1186/gb-2009-10-2-r18 Text en Copyright © 2009 Brower-Sinning 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
Brower-Sinning, Rachel
Carter, Donald M
Crevar, Corey J
Ghedin, Elodie
Ross, Ted M
Benos, Panayiotis V
The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus
title The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus
title_full The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus
title_fullStr The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus
title_full_unstemmed The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus
title_short The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus
title_sort role of rna folding free energy in the evolution of the polymerase genes of the influenza a virus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688270/
https://www.ncbi.nlm.nih.gov/pubmed/19216739
http://dx.doi.org/10.1186/gb-2009-10-2-r18
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