Proteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN response by poliovirus

Persistent Link:
http://hdl.handle.net/10150/610336
Title:
Proteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN response by poliovirus
Author:
Kotla, Swathi; Gustin, Kurt E.
Affiliation:
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania; Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix
Issue Date:
2015
Publisher:
BioMed Central
Citation:
Kotla and Gustin Virology Journal (2015) 12:158 DOI 10.1186/s12985-015-0393-2
Journal:
Virology Journal
Rights:
© 2015 Kotla and Gustin. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND: The type I interferon (IFN) response is a critical component of the innate immune response to infection by RNA viruses and is initiated via recognition of viral nucleic acids by RIG-like receptors (RLR). Engagement of these receptors in the cytoplasm initiates a signal transduction pathway leading to activation of the transcription factors NF-κB, ATF-2 and IRF-3 that coordinately upregulate transcription of type I IFN genes, such as that encoding IFN-β. In this study the impact of poliovirus infection on the type I interferon response has been examined. METHODS: The type I IFN response was assessed by measuring IFN-β mRNA levels using qRT-PCR and normalizing to levels of β-actin mRNA. The status of host factors involved in activation of the type I IFN response was examined by immunoblot, immunofluorescence microcopy and qRT-PCR. RESULTS: The results show that poliovirus infection results in induction of very low levels of IFN-β mRNA despite clear activation of NF-κB and ATF-2. In contrast, analysis of IRF-3 revealed no transcriptional induction of an IRF-3-responsive promoter or homodimerization of IRF-3 indicating it is not activated in poliovirus-infected cells. Exposure of poliovirus-infected cells to poly(I:C) results in lower levels of IFN-β mRNA synthesis and IRF-3 activation compared to mock-infected cells. Analysis of MDA-5 and IPS-1 revealed that these components of the RLR pathway were largely intact at times when the type I IFN response was suppressed. CONCLUSIONS: Collectively, these results demonstrate that poliovirus infection actively suppresses the host type I interferon response by blocking activation of IRF-3 and suggests that this is not mediated by cleavage of MDA-5 or IPS-1.
EISSN:
1743-422X
DOI:
10.1186/s12985-015-0393-2
Keywords:
Poliovirus; Enterovirus; Interferon; IRF-3; MDA-5; Type I interferon; RIG-like receptors
Version:
Final published version
Additional Links:
http://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0393-2

Full metadata record

DC FieldValue Language
dc.contributor.authorKotla, Swathien
dc.contributor.authorGustin, Kurt E.en
dc.date.accessioned2016-05-20T09:04:33Z-
dc.date.available2016-05-20T09:04:33Z-
dc.date.issued2015en
dc.identifier.citationKotla and Gustin Virology Journal (2015) 12:158 DOI 10.1186/s12985-015-0393-2en
dc.identifier.doi10.1186/s12985-015-0393-2en
dc.identifier.urihttp://hdl.handle.net/10150/610336-
dc.description.abstractBACKGROUND: The type I interferon (IFN) response is a critical component of the innate immune response to infection by RNA viruses and is initiated via recognition of viral nucleic acids by RIG-like receptors (RLR). Engagement of these receptors in the cytoplasm initiates a signal transduction pathway leading to activation of the transcription factors NF-κB, ATF-2 and IRF-3 that coordinately upregulate transcription of type I IFN genes, such as that encoding IFN-β. In this study the impact of poliovirus infection on the type I interferon response has been examined. METHODS: The type I IFN response was assessed by measuring IFN-β mRNA levels using qRT-PCR and normalizing to levels of β-actin mRNA. The status of host factors involved in activation of the type I IFN response was examined by immunoblot, immunofluorescence microcopy and qRT-PCR. RESULTS: The results show that poliovirus infection results in induction of very low levels of IFN-β mRNA despite clear activation of NF-κB and ATF-2. In contrast, analysis of IRF-3 revealed no transcriptional induction of an IRF-3-responsive promoter or homodimerization of IRF-3 indicating it is not activated in poliovirus-infected cells. Exposure of poliovirus-infected cells to poly(I:C) results in lower levels of IFN-β mRNA synthesis and IRF-3 activation compared to mock-infected cells. Analysis of MDA-5 and IPS-1 revealed that these components of the RLR pathway were largely intact at times when the type I IFN response was suppressed. CONCLUSIONS: Collectively, these results demonstrate that poliovirus infection actively suppresses the host type I interferon response by blocking activation of IRF-3 and suggests that this is not mediated by cleavage of MDA-5 or IPS-1.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0393-2en
dc.rights© 2015 Kotla and Gustin. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)en
dc.subjectPoliovirusen
dc.subjectEnterovirusen
dc.subjectInterferonen
dc.subjectIRF-3en
dc.subjectMDA-5en
dc.subjectType I interferonen
dc.subjectRIG-like receptorsen
dc.titleProteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN response by poliovirusen
dc.typeArticleen
dc.identifier.eissn1743-422Xen
dc.contributor.departmentDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvaniaen
dc.contributor.departmentDepartment of Basic Medical Sciences, University of Arizona College of Medicine-Phoenixen
dc.identifier.journalVirology Journalen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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