Journal
IMMUNITY
Volume 52, Issue 1, Pages 109-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2019.11.015
Keywords
-
Categories
Funding
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19000000]
- Ministry of Science and Technology of China [2016YFD0500207, 2016YFD0500407, 2018YFA0800702, 2016YFC0905902]
- National Natural Science Foundation of China [81930038, 81825011, 81630043, 81671572, 81571552, 81701569, 31700781, 81801575]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available