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Article: Saikosaponin D inhibits autophagy to suppress enterovirus A71 infection

TitleSaikosaponin D inhibits autophagy to suppress enterovirus A71 infection
Authors
Issue Date2019
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/sigtrans/
Citation
Signal Transduction and Targeted Therapy, 2019, v. 4, article no. 4 How to Cite?
AbstractThe dysregulation of autophagy, an evolutionarily conserved lysosomal degradation process, has been implicated in a wide variety of human diseases, and thus, small chemicals that modulate autophagy have therapeutic potential. Here, we assessed the ability of active components isolated from Bupleurum falcatum, a popular Chinese herb, to modulate autophagy. We found that saikosaponin D (SsD) and A (SsA) but not C (SsC) potently and reversibly inhibited the fusion of autophagosomes and lysosomes, resulting in the accumulation of autophagosomes, an increased lysosomal pH, and TFEB nuclear translocation. RAB5A knockdown or the expression of a dominant-negative RAB5 mutant significantly reduced the ability of SsD or SsA to block autophagy. Enterovirus A71 (EV-A71), the cause of hand-foot-mouth disease, has been shown to induce autophagy. We found that SsD potently inhibited EV-A71 RNA replication and subsequent viral protein synthesis, thereby preventing EV-A71-induced cell death. ATG5 knockdown inhibited EV-A71 viral protein synthesis, whereas autophagy induction by rapamycin promoted synthesis. Taken together, our data indicate that SsD and SsA are potent late-stage autophagy inhibitors that can be used to prevent EV-A71 infection.
Persistent Identifierhttp://hdl.handle.net/10722/274587
ISSN
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, C-
dc.contributor.authorHuang, L-
dc.contributor.authorSun, W-
dc.contributor.authorChen, Y-
dc.contributor.authorHe, ML-
dc.contributor.authorYue, J-
dc.contributor.authorBallard, HJ-
dc.date.accessioned2019-08-18T15:04:46Z-
dc.date.available2019-08-18T15:04:46Z-
dc.date.issued2019-
dc.identifier.citationSignal Transduction and Targeted Therapy, 2019, v. 4, article no. 4-
dc.identifier.issn2059-3635-
dc.identifier.urihttp://hdl.handle.net/10722/274587-
dc.description.abstractThe dysregulation of autophagy, an evolutionarily conserved lysosomal degradation process, has been implicated in a wide variety of human diseases, and thus, small chemicals that modulate autophagy have therapeutic potential. Here, we assessed the ability of active components isolated from Bupleurum falcatum, a popular Chinese herb, to modulate autophagy. We found that saikosaponin D (SsD) and A (SsA) but not C (SsC) potently and reversibly inhibited the fusion of autophagosomes and lysosomes, resulting in the accumulation of autophagosomes, an increased lysosomal pH, and TFEB nuclear translocation. RAB5A knockdown or the expression of a dominant-negative RAB5 mutant significantly reduced the ability of SsD or SsA to block autophagy. Enterovirus A71 (EV-A71), the cause of hand-foot-mouth disease, has been shown to induce autophagy. We found that SsD potently inhibited EV-A71 RNA replication and subsequent viral protein synthesis, thereby preventing EV-A71-induced cell death. ATG5 knockdown inhibited EV-A71 viral protein synthesis, whereas autophagy induction by rapamycin promoted synthesis. Taken together, our data indicate that SsD and SsA are potent late-stage autophagy inhibitors that can be used to prevent EV-A71 infection.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/sigtrans/-
dc.relation.ispartofSignal Transduction and Targeted Therapy-
dc.rightsThis is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI]-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSaikosaponin D inhibits autophagy to suppress enterovirus A71 infection-
dc.typeArticle-
dc.identifier.emailBallard, HJ: ballard@hkucc.hku.hk-
dc.identifier.authorityBallard, HJ=rp00367-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41392-019-0037-x-
dc.identifier.hkuros302278-
dc.identifier.volume4-
dc.identifier.spagearticle no. 4-
dc.identifier.epagearticle no. 4-
dc.identifier.isiWOS:000466923900001-
dc.publisher.placeUnited States-

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