p58IPK: A novel "CIHD" member of the host innate defense response against pathogenic virus infection

Alan G. Goodman, Jamie L. Fornek, Guruprasad R. Medigeshi, Lucy A. Perrone, Xinxia Peng, Matthew D. Dyer, Sean C. Proll, Sue E. Knoblaugh, Victoria S. Carter, Marcus J. Korth, Jay Nelson, Terrence M. Tumpey, Michael G. Katze

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

To support their replication, viruses take advantage of numerous cellular factors and processes. Recent large-scale screens have identified hundreds of such factors, yet little is known about how viruses exploit any of these. Influenza virus infection post-translationally activates P58IPK, a cellular inhibitor of the interferon-induced, dsRNA-activated eIF2α kinase, PKR. Here, we report that infection of P58IPK knockout mice with influenza virus resulted in increased lung pathology, immune cell apoptosis, PKR activation, and mortality. Analysis of lung transcriptional profiles, including those induced by the reconstructed 1918 pandemic virus, revealed increased expression of genes associated with the cell death, immune, and inflammatory responses. These experiments represent the first use of a mammalian infection model to demonstrate the role of P58IPK in the antiviral response. Our results suggest that P58IPK represents a new class of molecule, a cellular inhibitor of the host defense (CIHD), as P58 IPK is activated during virus infection to inhibit virus-induced apoptosis and inflammation to prolong host survival, even while prolonging viral replication.

Original languageEnglish (US)
Article numbere1000438
JournalPLoS Pathogens
Volume5
Issue number5
DOIs
Publication statusPublished - May 2009

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ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Goodman, A. G., Fornek, J. L., Medigeshi, G. R., Perrone, L. A., Peng, X., Dyer, M. D., ... Katze, M. G. (2009). p58IPK: A novel "CIHD" member of the host innate defense response against pathogenic virus infection. PLoS Pathogens, 5(5), [e1000438]. https://doi.org/10.1371/journal.ppat.1000438