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Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures
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....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468581/ https://www.ncbi.nlm.nih.gov/pubmed/36110293 http://dx.doi.org/10.3389/fmicb.2022.970501 |
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author | Liu, Yuanjia Zhang, Xinheng Liu, Zexin Huang, Li Jia, Weixin Lian, Xinlei Weng, Changjiang Zhang, Guihong Qi, Wenbao Chen, Jianxin |
author_facet | Liu, Yuanjia Zhang, Xinheng Liu, Zexin Huang, Li Jia, Weixin Lian, Xinlei Weng, Changjiang Zhang, Guihong Qi, Wenbao Chen, Jianxin |
author_sort | Liu, Yuanjia |
collection | PubMed |
description | 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; EC(50) = 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. |
format | Online Article Text |
id | pubmed-9468581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94685812022-09-14 Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures Liu, Yuanjia Zhang, Xinheng Liu, Zexin Huang, Li Jia, Weixin Lian, Xinlei Weng, Changjiang Zhang, Guihong Qi, Wenbao Chen, Jianxin Front Microbiol Microbiology 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; EC(50) = 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. Frontiers Media S.A. 2022-08-30 /pmc/articles/PMC9468581/ /pubmed/36110293 http://dx.doi.org/10.3389/fmicb.2022.970501 Text en Copyright © 2022 Liu, Zhang, Liu, Huang, Jia, Lian, Weng, Zhang, Qi and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Liu, Yuanjia Zhang, Xinheng Liu, Zexin Huang, Li Jia, Weixin Lian, Xinlei Weng, Changjiang Zhang, Guihong Qi, Wenbao Chen, Jianxin Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures |
title | Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures |
title_full | Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures |
title_fullStr | Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures |
title_full_unstemmed | Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures |
title_short | Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures |
title_sort | toosendanin suppresses african swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468581/ https://www.ncbi.nlm.nih.gov/pubmed/36110293 http://dx.doi.org/10.3389/fmicb.2022.970501 |
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