Host modulators of H1N1 cytopathogenicity

Samuel E. Ward, Hyun Seok Kim, Kakajan Komurov, Saurabh Mendiratta, Pei Ling Tsai, Mirco Schmolke, Neal Satterly, Balaji Manicassamy, Christian V. Forst, Michael G. Roth, Adolfo García-Sastre, Katarzyna M. Blazewska, Charles E. McKenna, Beatriz M. Fontoura, Michael A. White

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere39284
JournalPLoS One
Volume7
Issue number8
DOIs
Publication statusPublished - Aug 2 2012

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ward, S. E., Kim, H. S., Komurov, K., Mendiratta, S., Tsai, P. L., Schmolke, M., ... White, M. A. (2012). Host modulators of H1N1 cytopathogenicity. PLoS One, 7(8), [e39284]. https://doi.org/10.1371/journal.pone.0039284