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Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection
Zika virus (ZIKV) evolves non-structural proteins to evade immune response and ensure efficient replication in the host cells. Cholesterol metabolic enzyme 7-dehydrocholesterol reductase (DHCR7) was recently reported to impact innate immune responses in ZIKV infection. However, the vital non-structu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wuhan Institute of Virology, Chinese Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006206/ https://www.ncbi.nlm.nih.gov/pubmed/36182074 http://dx.doi.org/10.1016/j.virs.2022.09.009 |
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author | Chen, Weijie Li, Yukun Yu, Xiuling Wang, Zhenwei Wang, Wenbiao Rao, Menglan Li, Yongkui Luo, Zhen Zhang, Qiwei Liu, Jinbiao Wu, Jianguo |
author_facet | Chen, Weijie Li, Yukun Yu, Xiuling Wang, Zhenwei Wang, Wenbiao Rao, Menglan Li, Yongkui Luo, Zhen Zhang, Qiwei Liu, Jinbiao Wu, Jianguo |
author_sort | Chen, Weijie |
collection | PubMed |
description | Zika virus (ZIKV) evolves non-structural proteins to evade immune response and ensure efficient replication in the host cells. Cholesterol metabolic enzyme 7-dehydrocholesterol reductase (DHCR7) was recently reported to impact innate immune responses in ZIKV infection. However, the vital non-structural protein and mechanisms involved in DHCR7-mediated viral evasion are not well elucidated. In this study, we demonstrated that ZIKV infection facilitated DHCR7 expression. Notably, the upregulated DHCR7 in turn facilitated ZIKV infection and blocking DHCR7 suppressed ZIKV infection. Mechanically, ZIKV non-structural protein 4B (NS4B) interacted with DHCR7 to induce DHCR7 expression. Moreover, DHCR7 inhibited TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) phosphorylation, which resulted in the reduction of interferon-beta (IFN-β) and interferon-stimulated genes (ISGs) productions. Therefore, we propose that ZIKV NS4B binds to DHCR7 to repress TBK1 and IRF3 activation, which in turn inhibits IFN-β and ISGs, and thereby facilitating ZIKV evasion. This study broadens the insights on how viral non-structural proteins antagonize innate immunity to facilitate viral infection via cholesterol metabolic enzymes and intermediates. |
format | Online Article Text |
id | pubmed-10006206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wuhan Institute of Virology, Chinese Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-100062062023-03-12 Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection Chen, Weijie Li, Yukun Yu, Xiuling Wang, Zhenwei Wang, Wenbiao Rao, Menglan Li, Yongkui Luo, Zhen Zhang, Qiwei Liu, Jinbiao Wu, Jianguo Virol Sin Research Article Zika virus (ZIKV) evolves non-structural proteins to evade immune response and ensure efficient replication in the host cells. Cholesterol metabolic enzyme 7-dehydrocholesterol reductase (DHCR7) was recently reported to impact innate immune responses in ZIKV infection. However, the vital non-structural protein and mechanisms involved in DHCR7-mediated viral evasion are not well elucidated. In this study, we demonstrated that ZIKV infection facilitated DHCR7 expression. Notably, the upregulated DHCR7 in turn facilitated ZIKV infection and blocking DHCR7 suppressed ZIKV infection. Mechanically, ZIKV non-structural protein 4B (NS4B) interacted with DHCR7 to induce DHCR7 expression. Moreover, DHCR7 inhibited TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) phosphorylation, which resulted in the reduction of interferon-beta (IFN-β) and interferon-stimulated genes (ISGs) productions. Therefore, we propose that ZIKV NS4B binds to DHCR7 to repress TBK1 and IRF3 activation, which in turn inhibits IFN-β and ISGs, and thereby facilitating ZIKV evasion. This study broadens the insights on how viral non-structural proteins antagonize innate immunity to facilitate viral infection via cholesterol metabolic enzymes and intermediates. Wuhan Institute of Virology, Chinese Academy of Sciences 2022-09-29 /pmc/articles/PMC10006206/ /pubmed/36182074 http://dx.doi.org/10.1016/j.virs.2022.09.009 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Chen, Weijie Li, Yukun Yu, Xiuling Wang, Zhenwei Wang, Wenbiao Rao, Menglan Li, Yongkui Luo, Zhen Zhang, Qiwei Liu, Jinbiao Wu, Jianguo Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection |
title | Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection |
title_full | Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection |
title_fullStr | Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection |
title_full_unstemmed | Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection |
title_short | Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection |
title_sort | zika virus non-structural protein 4b interacts with dhcr7 to facilitate viral infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006206/ https://www.ncbi.nlm.nih.gov/pubmed/36182074 http://dx.doi.org/10.1016/j.virs.2022.09.009 |
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