Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465152/
https://www.ncbi.nlm.nih.gov/pubmed/36097162
http://dx.doi.org/10.1038/s41467-022-33041-1
_version_ 1784787730632278016
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.
author_facet 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.
author_sort Branche, Emilie
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9465152
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-94651522022-09-12 SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus 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. Nat Commun Article 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. Nature Publishing Group UK 2022-09-12 /pmc/articles/PMC9465152/ /pubmed/36097162 http://dx.doi.org/10.1038/s41467-022-33041-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
title SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
title_full SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
title_fullStr SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
title_full_unstemmed SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
title_short SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
title_sort srebp2-dependent lipid gene transcription enhances the infection of human dendritic cells by zika virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465152/
https://www.ncbi.nlm.nih.gov/pubmed/36097162
http://dx.doi.org/10.1038/s41467-022-33041-1
work_keys_str_mv AT brancheemilie srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT wangyingting srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT viramonteskarlam srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT vallscuevasjoanm srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT xiejialei srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT anasosabatizfernanda srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT shafeenorazizah srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT duttkesaschah srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT mcmillanrachele srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT clarkalexe srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT nguyenmichaeln srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT garretsonaaronf srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT cramesjanj srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT spannnathanj srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT zhuzhe srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT richjeremyn srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT spectordeborahh srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT bennerchristopher srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT shrestasujan srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus
AT carlinaaronf srebp2dependentlipidgenetranscriptionenhancestheinfectionofhumandendriticcellsbyzikavirus