AI Article Synopsis
- IRF3 is essential for producing type I interferons (IFN-α/β) and triggering antiviral immune responses.
- Viral infection causes the protein TOB1 to interact with IRF3, which then inhibits the transcription of the Ifnb1 gene essential for immune response in macrophages.
- Disabling Tob1 enhances the antiviral response and reduces viral replication, positioning TOB1 as a key negative regulator in the immune defense mechanism.
Article Abstract
Interferon regulatory factor 3 (IRF3) is a key transcription factor required for the secretion of type I interferons (IFN-α/β) and initiation of antiviral immune response. However, the negative feedback regulator of IRF3-directed antiviral response remains unknown. In this study, we demonstrated that viral infection induced the interaction of the transducer of ERBB2.1 (TOB1) with IRF3, which bound to the promoter region of Ifnb1 in macrophages. TOB1 inhibited Ifnb1 transcription by disrupting IRF3 binding and recruiting histone deacetylase 8 (HDAC8) to the Ifnb1 promoter region. Consequently, TOB1 attenuated IRF3-directed IFN-β expression in virus-infected macrophages. Tob1 deficiency enhanced antiviral response and suppressed viral replication in vivo. Thus, we identified TOB1 as a feedback inhibitor of host antiviral innate immune response and revealed a mechanism underlying viral immune escape.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463440 | PMC |
| http://dx.doi.org/10.1038/s42003-022-03911-x | DOI Listing |
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