Frequent outbreaks of viruses have caused a serious threat to public health. Previous evidence has revealed that DNA methylation is correlated with viral infections, but its role in innate immunity remains poorly investigated. Additionally, DNA methylation inhibitors promote IFN-I by upregulating endogenous retrovirus; however, studies of intrinsically demethylated tumors do not support this conclusion. This study found that Uhrf1 deficiency in myeloid cells significantly upregulated Ifnb expression, increasing resistance to viral infection. We performed whole-genome bisulfite sequencing and found that a single-nucleotide methylation site in the Ifnb promoter region disrupted IRF3 recruitment. We used site-specific mutant knock-in mice and a region-specific demethylation tool to confirm that this methylated site plays a critical role in regulating Ifnb expression and antiviral responses. These findings provide essential insight into DNA methylation in the regulation of the innate antiviral immune response.
Single-nucleotide methylation specifically represses type I interferon in antiviral innate immunity
Disclosures: The authors declare no competing interests exist.
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Zheng-jun Gao, Wen-ping Li, Xin-tao Mao, Tao Huang, Hao-li Wang, Yi-ning Li, Bao-qin Liu, Jiang-yan Zhong, Chai Renjie, Jin Jin, Yi-yuan Li; Single-nucleotide methylation specifically represses type I interferon in antiviral innate immunity. J Exp Med 1 March 2021; 218 (3): e20201798. doi: https://doi.org/10.1084/jem.20201798
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