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 Citations (Scopus)

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
StatePublished - May 2009

Fingerprint

Virus Diseases
Viruses
Orthomyxoviridae
Apoptosis
Lung
Pandemics
Virus Replication
Infection
Knockout Mice
Interferons
Antiviral Agents
Cell Death
Phosphotransferases
Pathology
Inflammation
Gene Expression
Mortality

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

p58IPK : A novel "CIHD" member of the host innate defense response against pathogenic virus infection. / Goodman, Alan G.; Fornek, Jamie L.; Medigeshi, Guruprasad R.; Perrone, Lucy A.; Peng, Xinxia; Dyer, Matthew D.; Proll, Sean C.; Knoblaugh, Sue E.; Carter, Victoria S.; Korth, Marcus J.; Nelson, Jay; Tumpey, Terrence M.; Katze, Michael G.

In: PLoS Pathogens, Vol. 5, No. 5, e1000438, 05.2009.

Research output: Contribution to journalArticle

Goodman, AG, Fornek, JL, Medigeshi, GR, Perrone, LA, Peng, X, Dyer, MD, Proll, SC, Knoblaugh, SE, Carter, VS, Korth, MJ, Nelson, J, Tumpey, TM & Katze, MG 2009, 'p58IPK: A novel "CIHD" member of the host innate defense response against pathogenic virus infection', PLoS Pathogens, vol. 5, no. 5, e1000438. https://doi.org/10.1371/journal.ppat.1000438
Goodman, Alan G. ; Fornek, Jamie L. ; Medigeshi, Guruprasad R. ; Perrone, Lucy A. ; Peng, Xinxia ; Dyer, Matthew D. ; Proll, Sean C. ; Knoblaugh, Sue E. ; Carter, Victoria S. ; Korth, Marcus J. ; Nelson, Jay ; Tumpey, Terrence M. ; Katze, Michael G. / p58IPK : A novel "CIHD" member of the host innate defense response against pathogenic virus infection. In: PLoS Pathogens. 2009 ; Vol. 5, No. 5.
@article{beb4e89e0fa842c8be19584c07eebb5b,
title = "p58IPK: A novel {"}CIHD{"} member of the host innate defense response against pathogenic virus infection",
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.",
author = "Goodman, {Alan G.} and Fornek, {Jamie L.} and Medigeshi, {Guruprasad R.} and Perrone, {Lucy A.} and Xinxia Peng and Dyer, {Matthew D.} and Proll, {Sean C.} and Knoblaugh, {Sue E.} and Carter, {Victoria S.} and Korth, {Marcus J.} and Jay Nelson and Tumpey, {Terrence M.} and Katze, {Michael G.}",
year = "2009",
month = "5",
doi = "10.1371/journal.ppat.1000438",
language = "English (US)",
volume = "5",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - p58IPK

T2 - A novel "CIHD" member of the host innate defense response against pathogenic virus infection

AU - Goodman, Alan G.

AU - Fornek, Jamie L.

AU - Medigeshi, Guruprasad R.

AU - Perrone, Lucy A.

AU - Peng, Xinxia

AU - Dyer, Matthew D.

AU - Proll, Sean C.

AU - Knoblaugh, Sue E.

AU - Carter, Victoria S.

AU - Korth, Marcus J.

AU - Nelson, Jay

AU - Tumpey, Terrence M.

AU - Katze, Michael G.

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67249119884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67249119884&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1000438

DO - 10.1371/journal.ppat.1000438

M3 - Article

C2 - 19461876

AN - SCOPUS:67249119884

VL - 5

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 5

M1 - e1000438

ER -