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 language | English (US) |
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Pages (from-to) | 40-48 |
Number of pages | 9 |
Journal | Virology |
Volume | 418 |
Issue number | 1 |
DOIs | |
State | Published - Sep 15 2011 |
Keywords
- Apoptosis
- B10.S
- IFNβ
- IL-6
- IRF-3
- ISG56
- Macrophages
- SJL/J
- TMEV
ASJC Scopus subject areas
- Virology