Xiao, Jun; Li, Weiyun; Zheng, Xin; Qi, Linlin; Wang, Hui; Zhang, Chi; Wan, Xiaopeng; Zheng, Yuxiao; Zhong, Ruiyue; Zhou, Xin; Lu, Yao; Li, Zhiqi; Qiu, Ying; Liu, Chang; Zhang, Fang; Zhang, Yanbo; Xu, Xiaoyan; Yang, Zhongzhou; Chen, Hualan; Zhai, Qiwei; Wei, Bin; Wang, Hongyan published the artcile< Targeting 7-Dehydrocholesterol Reductase Integrates Cholesterol Metabolism and IRF3 Activation to Eliminate Infection>, Application of C27H44O, the main research area is viral infection DHCR7 IRF3 TBK1 tamoxifen cholesterol metabolism; 7-DHC; AKT3; DHCR7; IRF3; cholesterol metabolism; infection; macrophage; type I IFN.
Recent work suggests that cholesterol metabolism impacts innate immune responses against infection. However, the key enzymes or the natural products and mechanisms involved are not well elucidated. Here, we have shown that upon DNA and RNA viral infection, macrophages reduced 7-dehydrocholesterol reductase (DHCR7) expression. DHCR7 deficiency or treatment with the natural product 7-dehydrocholesterol (7-DHC) could specifically promote phosphorylation of IRF3 (not TBK1) and enhance type I interferon (IFN-I) production in macrophages. We further elucidated that viral infection or 7-DHC treatment enhanced AKT3 expression and activation. AKT3 directly bound and phosphorylated IRF3 at Ser385, together with TBK1-induced phosphorylation of IRF3 Ser386, to achieve IRF3 dimerization. Deletion of DHCR7 and the DHCR7 inhibitors including AY9944 and the chemotherapy drug tamoxifen promoted clearance of Zika virus and multiple viruses in vitro or in vivo. Taken together, we propose that the DHCR7 inhibitors and 7-DHC are potential therapeutics against emerging or highly pathogenic viruses.
Immunity published new progress about Cell membrane. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Application of C27H44O.
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