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....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.970501/full |
| _version_ | 1798035982483718144 |
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| author | Yuanjia Liu Xinheng Zhang Zexin Liu Li Huang Weixin Jia Xinlei Lian Changjiang Weng Guihong Zhang Wenbao Qi Jianxin Chen |
| author_facet | Yuanjia Liu Xinheng Zhang Zexin Liu Li Huang Weixin Jia Xinlei Lian Changjiang Weng Guihong Zhang Wenbao Qi Jianxin Chen |
| author_sort | Yuanjia Liu |
| collection | DOAJ |
| 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; 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. |
| first_indexed | 2024-04-11T21:06:09Z |
| format | Article |
| id | doaj.art-a37e1b4b6f974a49b0e4466040ced1aa |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-11T21:06:09Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-a37e1b4b6f974a49b0e4466040ced1aa2022-12-22T04:03:20ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-08-011310.3389/fmicb.2022.970501970501Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage culturesYuanjia Liu0Xinheng Zhang1Zexin Liu2Li Huang3Weixin Jia4Xinlei Lian5Changjiang Weng6Guihong Zhang7Wenbao Qi8Jianxin Chen9Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaCollege of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaAfrican Swine Fever Regional Laboratory of China (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaAfrican Swine Fever Regional Laboratory of China (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaAfrican Swine Fever Regional Laboratory of China (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaAfrican 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.https://www.frontiersin.org/articles/10.3389/fmicb.2022.970501/fullAfrican swine fever virustoosendaninantiviral activityporcine alveolar macrophagesinterferon regulatory factor 1 |
| spellingShingle | Yuanjia Liu Xinheng Zhang Zexin Liu Li Huang Weixin Jia Xinlei Lian Changjiang Weng Guihong Zhang Wenbao Qi Jianxin Chen Toosendanin suppresses African swine fever virus replication through upregulating interferon regulatory factor 1 in porcine alveolar macrophage cultures Frontiers in Microbiology African swine fever virus toosendanin antiviral activity porcine alveolar macrophages interferon regulatory factor 1 |
| 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 | African swine fever virus toosendanin antiviral activity porcine alveolar macrophages interferon regulatory factor 1 |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.970501/full |
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