SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus

Emilie Branche, Ying-Ting Wang, Karla M. Viramontes, Joan M. Valls Cuevas, Jialei Xie, Fernanda Ana-Sosa-Batiz, Norazizah Shafee, Sascha H. Duttke, Rachel E. McMillan, Alex E. Clark, Michael N. Nguyen, Aaron F. Garretson, Jan J. Crames, Nathan J. Spann, Zhe Zhu, Jeremy N. Rich, Deborah H. Spector, Christopher Benner, Sujan Shresta () and Aaron F. Carlin ()
Additional contact information
Emilie Branche: La Jolla Institute for Immunology
Ying-Ting Wang: La Jolla Institute for Immunology
Karla M. Viramontes: La Jolla Institute for Immunology
Joan M. Valls Cuevas: La Jolla Institute for Immunology
Jialei Xie: University of California, San Diego
Fernanda Ana-Sosa-Batiz: La Jolla Institute for Immunology
Norazizah Shafee: La Jolla Institute for Immunology
Sascha H. Duttke: Washington State University
Rachel E. McMillan: University of California, San Diego
Alex E. Clark: University of California, San Diego
Michael N. Nguyen: La Jolla Institute for Immunology
Aaron F. Garretson: University of California, San Diego
Jan J. Crames: La Jolla Institute for Immunology
Nathan J. Spann: University of California San Diego
Zhe Zhu: University of California San Diego
Jeremy N. Rich: University of California San Diego
Deborah H. Spector: University of California San Diego
Christopher Benner: University of California, San Diego
Sujan Shresta: La Jolla Institute for Immunology
Aaron F. Carlin: University of California, San Diego

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33041-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33041-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33041-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().