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Host Modulators of H1N1 Cytopathogenicity
Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolut...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410888/ https://www.ncbi.nlm.nih.gov/pubmed/22876275 http://dx.doi.org/10.1371/journal.pone.0039284 |
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author | Ward, Samuel E. Kim, Hyun Seok Komurov, Kakajan Mendiratta, Saurabh Tsai, Pei-Ling Schmolke, Mirco Satterly, Neal Manicassamy, Balaji Forst, Christian V. Roth, Michael G. García-Sastre, Adolfo Blazewska, Katarzyna M. McKenna, Charles E. Fontoura, Beatriz M. White, Michael A. |
author_facet | Ward, Samuel E. Kim, Hyun Seok Komurov, Kakajan Mendiratta, Saurabh Tsai, Pei-Ling Schmolke, Mirco Satterly, Neal Manicassamy, Balaji Forst, Christian V. Roth, Michael G. García-Sastre, Adolfo Blazewska, Katarzyna M. McKenna, Charles E. Fontoura, Beatriz M. White, Michael A. |
author_sort | Ward, Samuel E. |
collection | PubMed |
description | Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors. |
format | Online Article Text |
id | pubmed-3410888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34108882012-08-08 Host Modulators of H1N1 Cytopathogenicity Ward, Samuel E. Kim, Hyun Seok Komurov, Kakajan Mendiratta, Saurabh Tsai, Pei-Ling Schmolke, Mirco Satterly, Neal Manicassamy, Balaji Forst, Christian V. Roth, Michael G. García-Sastre, Adolfo Blazewska, Katarzyna M. McKenna, Charles E. Fontoura, Beatriz M. White, Michael A. PLoS One Research Article Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors. Public Library of Science 2012-08-02 /pmc/articles/PMC3410888/ /pubmed/22876275 http://dx.doi.org/10.1371/journal.pone.0039284 Text en © 2012 Ward et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ward, Samuel E. Kim, Hyun Seok Komurov, Kakajan Mendiratta, Saurabh Tsai, Pei-Ling Schmolke, Mirco Satterly, Neal Manicassamy, Balaji Forst, Christian V. Roth, Michael G. García-Sastre, Adolfo Blazewska, Katarzyna M. McKenna, Charles E. Fontoura, Beatriz M. White, Michael A. Host Modulators of H1N1 Cytopathogenicity |
title | Host Modulators of H1N1 Cytopathogenicity |
title_full | Host Modulators of H1N1 Cytopathogenicity |
title_fullStr | Host Modulators of H1N1 Cytopathogenicity |
title_full_unstemmed | Host Modulators of H1N1 Cytopathogenicity |
title_short | Host Modulators of H1N1 Cytopathogenicity |
title_sort | host modulators of h1n1 cytopathogenicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410888/ https://www.ncbi.nlm.nih.gov/pubmed/22876275 http://dx.doi.org/10.1371/journal.pone.0039284 |
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