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- Title
SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus.
- Authors
Branche, Emilie; Wang, Ying-Ting; Viramontes, Karla M.; Valls Cuevas, Joan M.; Xie, Jialei; Ana-Sosa-Batiz, Fernanda; Shafee, Norazizah; Duttke, Sascha H.; McMillan, Rachel E.; Clark, Alex E.; Nguyen, Michael N.; Garretson, Aaron F.; Crames, Jan J.; Spann, Nathan J.; Zhu, Zhe; Rich, Jeremy N.; Spector, Deborah H.; Benner, Christopher; Shresta, Sujan; Carlin, Aaron F.
- Abstract
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. 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.
- Subjects
ZIKA virus; STEROL regulatory element-binding proteins; ZIKA virus infections; DENDRITIC cells; TRANSCRIPTION factors; GENE silencing; LIPIDS
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-33041-1