학술논문
SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
Document Type
article
Author
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
Source
Nature Communications. 13(1)
Subject
Language
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.