Human rhinovirus attenuates the type I interferon response by disrupting activation of interferon regulatory factor 3

Tao Peng, Swathi Kotla, Roger E. Bumgarner, Kurt E Gustin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.

Original languageEnglish (US)
Pages (from-to)5021-5031
Number of pages11
JournalJournal of Virology
Volume80
Issue number10
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

Human rhinovirus
Interferon Regulatory Factor-3
Rhinovirus
Interferon Type I
interferons
Enterovirus
Interferons
Infection
Messenger RNA
infection
Alveolar Epithelial Cells
Double-Stranded RNA
cells
interferon regulatory factor-3
HeLa Cells
Antiviral Agents
double-stranded RNA
Transcription Factors
Viruses
epithelial cells

ASJC Scopus subject areas

  • Immunology

Cite this

Human rhinovirus attenuates the type I interferon response by disrupting activation of interferon regulatory factor 3. / Peng, Tao; Kotla, Swathi; Bumgarner, Roger E.; Gustin, Kurt E.

In: Journal of Virology, Vol. 80, No. 10, 05.2006, p. 5021-5031.

Research output: Contribution to journalArticle

@article{bfff08e15c1146d7a9a63649260292b9,
title = "Human rhinovirus attenuates the type I interferon response by disrupting activation of interferon regulatory factor 3",
abstract = "The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.",
author = "Tao Peng and Swathi Kotla and Bumgarner, {Roger E.} and Gustin, {Kurt E}",
year = "2006",
month = "5",
doi = "10.1128/JVI.80.10.5021-5031.2006",
language = "English (US)",
volume = "80",
pages = "5021--5031",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "10",

}

TY - JOUR

T1 - Human rhinovirus attenuates the type I interferon response by disrupting activation of interferon regulatory factor 3

AU - Peng, Tao

AU - Kotla, Swathi

AU - Bumgarner, Roger E.

AU - Gustin, Kurt E

PY - 2006/5

Y1 - 2006/5

N2 - The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.

AB - The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.

UR - http://www.scopus.com/inward/record.url?scp=33646450399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646450399&partnerID=8YFLogxK

U2 - 10.1128/JVI.80.10.5021-5031.2006

DO - 10.1128/JVI.80.10.5021-5031.2006

M3 - Article

VL - 80

SP - 5021

EP - 5031

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 10

ER -