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Article: SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target

TitleSREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target
Authors
Issue Date2019
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2019, v. 10, article no. 120 How to Cite?
AbstractViruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.
Persistent Identifierhttp://hdl.handle.net/10722/271920
ISSN
2017 Impact Factor: 12.353
2015 SCImago Journal Rankings: 6.539
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYuan, S-
dc.contributor.authorChu, H-
dc.contributor.authorChan, JFW-
dc.contributor.authorYe, Z-
dc.contributor.authorWen, L-
dc.contributor.authorYan, B-
dc.contributor.authorLai, PM-
dc.contributor.authorTee, KM-
dc.contributor.authorHuang, J-
dc.contributor.authorChen, D-
dc.contributor.authorLi, C-
dc.contributor.authorZhao, X-
dc.contributor.authorYang, D-
dc.contributor.authorChiu, MC-
dc.contributor.authorYip, C-
dc.contributor.authorPoon, VKM-
dc.contributor.authorChan, CCS-
dc.contributor.authorSze, KH-
dc.contributor.authorZhou, J-
dc.contributor.authorChan, IHY-
dc.contributor.authorKok, KH-
dc.contributor.authorTo, KKW-
dc.contributor.authorKao, RYT-
dc.contributor.authorLau, JYN-
dc.contributor.authorJin, D-
dc.contributor.authorPerlman, S-
dc.contributor.authorYuen, KY-
dc.date.accessioned2019-07-20T10:32:06Z-
dc.date.available2019-07-20T10:32:06Z-
dc.date.issued2019-
dc.identifier.citationNature Communications, 2019, v. 10, article no. 120-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/271920-
dc.description.abstractViruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target-
dc.typeArticle-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailYe, Z: zwye@hku.hk-
dc.identifier.emailYan, B: ybp1205@hku.hk-
dc.identifier.emailLai, PM: vangor@hku.hk-
dc.identifier.emailHuang, J: huangjj@hku.hk-
dc.identifier.emailChen, D: chendd@hku.hk-
dc.identifier.emailLi, C: licun@hku.hk-
dc.identifier.emailPoon, VKM: vinpoon@hku.hk-
dc.identifier.emailChan, CCS: cschan@hku.hk-
dc.identifier.emailSze, KH: khsze@hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authoritySze, KH=rp00785-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityKao, RYT=rp00481-
dc.identifier.authorityJin, D=rp00452-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-018-08015-x-
dc.identifier.pmid30631056-
dc.identifier.pmcidPMC6328544-
dc.identifier.scopuseid_2-s2.0-85059829725-
dc.identifier.hkuros298541-
dc.identifier.volume10-
dc.identifier.spagearticle no. 120-
dc.identifier.epagearticle no. 120-
dc.identifier.isiWOS:000455354800017-
dc.publisher.placeUnited Kingdom-
dc.identifier.f1000734828056-

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