IRF3 polymorphisms induce different innate anti-Theiler's virus immune responses in RAW264.7 macrophages

Tyler C. Moore, Fahd M. Al-Salleeh, Deborah M Brown, Thomas M Petro

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Persistent viral infections can lead to disease such as myocarditis. Theiler's murine encephalomyelitis virus (TMEV) infects macrophages of SJL/J (H-2s) mice establishing persistent infections leading to demyelinating disease. In contrast macrophages from B10.S (H-2s) mice clear TMEV. Activation of the transcription factor IRF3 induces IFNβ, ISG56, and apoptosis for viral clearance, but also inflammatory cytokines, such as IL-23 and IL6, which contribute to disease. Here we identify polymorphisms in the IRF3 of SJL/J versus B10.S mice that are located in DNA binding, nuclear localization, and autoinhibitory domains. SJL-IRF3 expression in RAW264.7 macrophage cells with or without TMEV infection decreased IL-23p19 promoter activity compared with B10S-IRF3. In contrast SJL-IRF3 increased IL-6, ISG56 and IFNβ in response to TMEV. B10S-IRF3 expression augmented apoptotic caspase activation and decreased viral RNA in TMEV-infected macrophages while SJL-IRF3 increased viral replication with less caspase activation. Therefore IRF3 polymorphisms contribute to viral persistence and altered cytokine expression.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalVirology
Volume418
Issue number1
DOIs
StatePublished - Sep 15 2011

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Theilovirus
Macrophages
Virus Diseases
Caspases
Interleukin-6
Interleukin-23 Subunit p19
Cytokines
Interleukin-23
Myocarditis
Viral RNA
Demyelinating Diseases
Transcription Factors
Apoptosis
DNA
Infection

Keywords

  • Apoptosis
  • B10.S
  • IFNβ
  • IL-6
  • IRF-3
  • ISG56
  • Macrophages
  • SJL/J
  • TMEV

ASJC Scopus subject areas

  • Virology

Cite this

IRF3 polymorphisms induce different innate anti-Theiler's virus immune responses in RAW264.7 macrophages. / Moore, Tyler C.; Al-Salleeh, Fahd M.; Brown, Deborah M; Petro, Thomas M.

In: Virology, Vol. 418, No. 1, 15.09.2011, p. 40-48.

Research output: Contribution to journalArticle

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