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

Swathi Kotla, Kurt E. Gustin

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Article number158
JournalVirology Journal
Volume12
Issue number1
DOIs
StatePublished - Oct 6 2015

Keywords

  • Enterovirus
  • IRF-3
  • Interferon
  • MDA-5
  • Poliovirus
  • RIG-like receptors
  • Type I interferon

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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