期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-33041-1
关键词
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资金
- Career Award for Medical Scientists from the Burroughs Wellcome Fund
- NIH [K08 AI130381, K99/R00 GM135515, CA238662, CA197718, NS103434, R01 AI116813, R01 AI153500, R01 NS106387, R21 AI140063, GM134366]
- NIAID [R01 AI129846]
- National Institute for General Medical Sciences [T32 GM008666]
- National Institutes of Health SIG grant [S10 OD026929]
- Common Fund of the Office of the Director of the National Institutes of Health
- NCI
- NHGRI
- NHLBI
- NIDA
- NIMH
- NINDS
The study reveals that ZIKV infection alters the expression of inflammation- and metabolism-related genes to modulate the functions of dendritic cells.
Zika virus (ZIKV) infection suppresses the induction of dendritic cell (DC)-derived immunity, but the underlying mechanistical insights are still lacking. Here the authors show, using in vitro systems profiling of DC transcriptome and epigenome, that ZIKV specifically alters SREBP2-related expression of inflammation- and metabolism-related genes to modulate DC functions. The emergence of Zika virus (ZIKV) as a global health threat has highlighted the unmet need for ZIKV-specific vaccines and antiviral treatments. ZIKV infects dendritic cells (DC), which have pivotal functions in activating innate and adaptive antiviral responses; however, the mechanisms by which DC function is subverted to establish ZIKV infection are unclear. Here we develop a genomics profiling method that enables discrete analysis of ZIKV-infected versus neighboring, uninfected primary human DCs to increase the sensitivity and specificity with which ZIKV-modulated pathways can be identified. The results show that ZIKV infection specifically increases the expression of genes enriched for lipid metabolism-related functions. ZIKV infection also increases the recruitment of sterol regulatory element-binding protein (SREBP) transcription factors to lipid gene promoters, while pharmacologic inhibition or genetic silencing of SREBP2 suppresses ZIKV infection of DCs. Our data thus identify SREBP2-activated transcription as a mechanism for promoting ZIKV infection amenable to therapeutic targeting.
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