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Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures

文献类型： 外文期刊

作者： Liu Y.; Zhang X.; Liu Z.; Huang L.; Jia W.; Lian X.; Weng C.; Zhang G.; Qi W.; Chen J.

作者机构：

关键词： chemical compound; fibrinogen; interferon regulatory factor 1; saponin; Toosendanin; unclassified drug; African swine fever; African swine fever virus; animal cell; animal experiment; animal tissue; antimicrobial activity; antimicrobial therapy; antiviral activity; Article; cell viability; chemoluminescence; controlled study; cytotoxic concentration; cytotoxicity assay; DNA extraction; down regulation; gene expression; genetic analysis; genetic transcription; genetic transfection; immunofluorescence; lung alveolus macrophage; mouse; MTT assay; nonhuman; optical density; PK-15 cell line; polymerase chain reaction; protein expression; real time reverse transcription polymerase chain reaction; RNA extraction; RNA interference; signal transduction; virus entry; virus load; virus particle; virus release; virus replication; Western blotting

期刊名称： Frontiers in Microbiology

ISSN： 1664-302X

年卷期： 2022 年 13 卷

页码：

摘要： African swine fever virus (ASFV) is a highly infectious and lethal swine pathogen that causes severe socio-economic consequences in affected countries. Unfortunately, effective vaccine for combating ASF is unavailable so far, and the prevention and control strategies for ASFV are still very limited. Toosendanin (TSN), a triterpenoid saponin extracted from the medicinal herb Melia toosendan Sieb. Et Zucc, has been demonstrated to possess analgesic, anti-inflammatory, anti-botulism and anti-microbial activities, and was used clinically as an anthelmintic, while the antiviral effect of TSN on ASFV has not been reported. In this study, we revealed that TSN exhibited a potent inhibitory effect on ASFV GZ201801-38 strain in porcine alveolar macrophages (PAMs; EC50 = 0.085 μM, SI = 365) in a dose-dependent manner. TSN showed robust antiviral activity in different doses of ASFV infection and reduced the transcription and translation levels of ASFV p30 protein, viral genomic DNA quantity as well as viral titer at 24 and 48 h post-infection. In addition, TSN did not affect virion attachment and release but intervened in its internalization in PAMs. Further investigations disclosed that TSN played its antiviral role by upregulating the host IFN-stimulated gene (ISG) IRF1 rather than by directly inactivating the virus particles. Overall, our results suggest that TSN is an effective antiviral agent against ASFV replication in vitro and may have the potential for clinical use. Copyright © 2022 Liu, Zhang, Liu, Huang, Jia, Lian, Weng, Zhang, Qi and Chen.

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