Identification of an NF-κB-dependent gene network in cells infected by mammalian reovirus

Scan M. O'Donnell, Geoffrey H. Holm, Janene M. Pierce, Bing Tian, Melissa J. Watson, Ravi S. Chari, Dean W. Ballard, Allan R. Brasier, Terence S. Dermody

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Reovirus infection activates NF-κB;, which leads to programmed cell death in cultured cells and in the murine central nervous system. However, little is known about how NF-κB elicits this cellular response. To identify host genes activated by NF-κB following reovirus infection, we used HeLa cells engineered to express a degradation-resistant mutant of IκBα (mIκBα) under the control of an inducible promoter. Induction of mIκBα inhibited the activation of NF-κB and blocked the expression of NF-KB-responsive genes. RNA extracted from infected and uninfected cells was used in high-density oligonucleotide microarrays to examine the expression of constitutively activated genes and reovirus-stimulated genes in the presence and absence of an intact NF-κB signaling axis. Comparison of the microarray profiles revealed that the expression of 176 genes was significantly altered in the presence of mIκBα Of these genes, 64 were constitutive and not regulated by reovirus, and 112 were induced in response to reovirus infection. NF-KB-regulated genes could be grouped into four distinct gene clusters that were temporally regulated. Gene ontology analysis identified biological processes that were significantly overrepresented in the reovirus-induced genes under NF-κ;B control. These processes include the antiviral innate immune response, cell proliferation, response to DNA damage, and taxis. Comparison with previously identified NF-KB-dependent gene networks induced by other stimuli, including respiratory syncytial virus, Epstein-Barr virus, tumor necrosis factor alpha, and heart disease, revealed a number of common components, including CCL5/RANTES, CXCL1/GRO-α, TNFAIP3/A20, and interleukin-6. Together, these results suggest a genetic program for reovirus-induced apoptosis involving NF-κB-directed expression of cellular genes that activate death signaling pathways in infected cells.

Original languageEnglish (US)
Pages (from-to)1077-1086
Number of pages10
JournalJournal of Virology
Volume80
Issue number3
DOIs
StatePublished - Feb 2006

Fingerprint

Reoviridae
Gene Regulatory Networks
Reoviridae Infections
Genes
genes
cells
mutants
Biological Phenomena
Gene Expression
Chemokine CCL5
Gene Ontology
apoptosis
Respiratory Syncytial Viruses
infection
Multigene Family
gene regulatory networks
Oligonucleotide Array Sequence Analysis
Human Herpesvirus 4
Human herpesvirus 4
HeLa Cells

ASJC Scopus subject areas

  • Immunology

Cite this

O'Donnell, S. M., Holm, G. H., Pierce, J. M., Tian, B., Watson, M. J., Chari, R. S., ... Dermody, T. S. (2006). Identification of an NF-κB-dependent gene network in cells infected by mammalian reovirus. Journal of Virology, 80(3), 1077-1086. https://doi.org/10.1128/JVI.80.3.1077-1086.2006

Identification of an NF-κB-dependent gene network in cells infected by mammalian reovirus. / O'Donnell, Scan M.; Holm, Geoffrey H.; Pierce, Janene M.; Tian, Bing; Watson, Melissa J.; Chari, Ravi S.; Ballard, Dean W.; Brasier, Allan R.; Dermody, Terence S.

In: Journal of Virology, Vol. 80, No. 3, 02.2006, p. 1077-1086.

Research output: Contribution to journalArticle

O'Donnell, SM, Holm, GH, Pierce, JM, Tian, B, Watson, MJ, Chari, RS, Ballard, DW, Brasier, AR & Dermody, TS 2006, 'Identification of an NF-κB-dependent gene network in cells infected by mammalian reovirus', Journal of Virology, vol. 80, no. 3, pp. 1077-1086. https://doi.org/10.1128/JVI.80.3.1077-1086.2006
O'Donnell, Scan M. ; Holm, Geoffrey H. ; Pierce, Janene M. ; Tian, Bing ; Watson, Melissa J. ; Chari, Ravi S. ; Ballard, Dean W. ; Brasier, Allan R. ; Dermody, Terence S. / Identification of an NF-κB-dependent gene network in cells infected by mammalian reovirus. In: Journal of Virology. 2006 ; Vol. 80, No. 3. pp. 1077-1086.
@article{2c7d075c554d4b46856dea43e22a609a,
title = "Identification of an NF-κB-dependent gene network in cells infected by mammalian reovirus",
abstract = "Reovirus infection activates NF-κB;, which leads to programmed cell death in cultured cells and in the murine central nervous system. However, little is known about how NF-κB elicits this cellular response. To identify host genes activated by NF-κB following reovirus infection, we used HeLa cells engineered to express a degradation-resistant mutant of IκBα (mIκBα) under the control of an inducible promoter. Induction of mIκBα inhibited the activation of NF-κB and blocked the expression of NF-KB-responsive genes. RNA extracted from infected and uninfected cells was used in high-density oligonucleotide microarrays to examine the expression of constitutively activated genes and reovirus-stimulated genes in the presence and absence of an intact NF-κB signaling axis. Comparison of the microarray profiles revealed that the expression of 176 genes was significantly altered in the presence of mIκBα Of these genes, 64 were constitutive and not regulated by reovirus, and 112 were induced in response to reovirus infection. NF-KB-regulated genes could be grouped into four distinct gene clusters that were temporally regulated. Gene ontology analysis identified biological processes that were significantly overrepresented in the reovirus-induced genes under NF-κ;B control. These processes include the antiviral innate immune response, cell proliferation, response to DNA damage, and taxis. Comparison with previously identified NF-KB-dependent gene networks induced by other stimuli, including respiratory syncytial virus, Epstein-Barr virus, tumor necrosis factor alpha, and heart disease, revealed a number of common components, including CCL5/RANTES, CXCL1/GRO-α, TNFAIP3/A20, and interleukin-6. Together, these results suggest a genetic program for reovirus-induced apoptosis involving NF-κB-directed expression of cellular genes that activate death signaling pathways in infected cells.",
author = "O'Donnell, {Scan M.} and Holm, {Geoffrey H.} and Pierce, {Janene M.} and Bing Tian and Watson, {Melissa J.} and Chari, {Ravi S.} and Ballard, {Dean W.} and Brasier, {Allan R.} and Dermody, {Terence S.}",
year = "2006",
month = "2",
doi = "10.1128/JVI.80.3.1077-1086.2006",
language = "English (US)",
volume = "80",
pages = "1077--1086",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Identification of an NF-κB-dependent gene network in cells infected by mammalian reovirus

AU - O'Donnell, Scan M.

AU - Holm, Geoffrey H.

AU - Pierce, Janene M.

AU - Tian, Bing

AU - Watson, Melissa J.

AU - Chari, Ravi S.

AU - Ballard, Dean W.

AU - Brasier, Allan R.

AU - Dermody, Terence S.

PY - 2006/2

Y1 - 2006/2

N2 - Reovirus infection activates NF-κB;, which leads to programmed cell death in cultured cells and in the murine central nervous system. However, little is known about how NF-κB elicits this cellular response. To identify host genes activated by NF-κB following reovirus infection, we used HeLa cells engineered to express a degradation-resistant mutant of IκBα (mIκBα) under the control of an inducible promoter. Induction of mIκBα inhibited the activation of NF-κB and blocked the expression of NF-KB-responsive genes. RNA extracted from infected and uninfected cells was used in high-density oligonucleotide microarrays to examine the expression of constitutively activated genes and reovirus-stimulated genes in the presence and absence of an intact NF-κB signaling axis. Comparison of the microarray profiles revealed that the expression of 176 genes was significantly altered in the presence of mIκBα Of these genes, 64 were constitutive and not regulated by reovirus, and 112 were induced in response to reovirus infection. NF-KB-regulated genes could be grouped into four distinct gene clusters that were temporally regulated. Gene ontology analysis identified biological processes that were significantly overrepresented in the reovirus-induced genes under NF-κ;B control. These processes include the antiviral innate immune response, cell proliferation, response to DNA damage, and taxis. Comparison with previously identified NF-KB-dependent gene networks induced by other stimuli, including respiratory syncytial virus, Epstein-Barr virus, tumor necrosis factor alpha, and heart disease, revealed a number of common components, including CCL5/RANTES, CXCL1/GRO-α, TNFAIP3/A20, and interleukin-6. Together, these results suggest a genetic program for reovirus-induced apoptosis involving NF-κB-directed expression of cellular genes that activate death signaling pathways in infected cells.

AB - Reovirus infection activates NF-κB;, which leads to programmed cell death in cultured cells and in the murine central nervous system. However, little is known about how NF-κB elicits this cellular response. To identify host genes activated by NF-κB following reovirus infection, we used HeLa cells engineered to express a degradation-resistant mutant of IκBα (mIκBα) under the control of an inducible promoter. Induction of mIκBα inhibited the activation of NF-κB and blocked the expression of NF-KB-responsive genes. RNA extracted from infected and uninfected cells was used in high-density oligonucleotide microarrays to examine the expression of constitutively activated genes and reovirus-stimulated genes in the presence and absence of an intact NF-κB signaling axis. Comparison of the microarray profiles revealed that the expression of 176 genes was significantly altered in the presence of mIκBα Of these genes, 64 were constitutive and not regulated by reovirus, and 112 were induced in response to reovirus infection. NF-KB-regulated genes could be grouped into four distinct gene clusters that were temporally regulated. Gene ontology analysis identified biological processes that were significantly overrepresented in the reovirus-induced genes under NF-κ;B control. These processes include the antiviral innate immune response, cell proliferation, response to DNA damage, and taxis. Comparison with previously identified NF-KB-dependent gene networks induced by other stimuli, including respiratory syncytial virus, Epstein-Barr virus, tumor necrosis factor alpha, and heart disease, revealed a number of common components, including CCL5/RANTES, CXCL1/GRO-α, TNFAIP3/A20, and interleukin-6. Together, these results suggest a genetic program for reovirus-induced apoptosis involving NF-κB-directed expression of cellular genes that activate death signaling pathways in infected cells.

UR - http://www.scopus.com/inward/record.url?scp=31144460826&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31144460826&partnerID=8YFLogxK

U2 - 10.1128/JVI.80.3.1077-1086.2006

DO - 10.1128/JVI.80.3.1077-1086.2006

M3 - Article

VL - 80

SP - 1077

EP - 1086

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -