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.
Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/610336 |
Date | January 2015 |
Creators | Kotla, Swathi, Gustin, Kurt E. |
Contributors | Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix |
Publisher | BioMed Central |
Source Sets | University of Arizona |
Language | English |
Detected Language | English |
Type | Article |
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/) |
Relation | http://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0393-2 |
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