Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model
IntroductionPorcine circovirus type 2 (PCV2) is an important pathogen that causes diarrhea in nursery and fattening pigs, resulting in huge economic losses for commercial pig farms. Protective efficacy of vaccines is compromised by mutations in pathogens. There is an urgent need to articulate the me...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1455049/full |
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| author | Hong Wang Hong Wang Na Sun Panpan Sun Hua Zhang Wei Yin Xiaozhong Zheng Kuohai Fan Kuohai Fan Yaogui Sun Hongquan Li |
| author_facet | Hong Wang Hong Wang Na Sun Panpan Sun Hua Zhang Wei Yin Xiaozhong Zheng Kuohai Fan Kuohai Fan Yaogui Sun Hongquan Li |
| author_sort | Hong Wang |
| collection | DOAJ |
| description | IntroductionPorcine circovirus type 2 (PCV2) is an important pathogen that causes diarrhea in nursery and fattening pigs, resulting in huge economic losses for commercial pig farms. Protective efficacy of vaccines is compromised by mutations in pathogens. There is an urgent need to articulate the mechanism by which PCV2 destroys the host’s intestinal mucosal barrier and to find effective therapeutic drugs. Increasing attention has been paid to the natural antiviral compounds extracted from traditional Chinese medicines. In the present study, we investigated the role of Matrine in mitigating PCV2-induced intestinal damage and enhancing autophagy as a potential therapeutic strategy in mice.MethodsA total of 40 female, specific-pathogen-free-grade Kunming mice were randomly divided into four groups with 10 mice in each group: control, PCV2 infection, Matrine treatment (40 mg/kg Matrine), and Ribavirin treatment (40 mg/kg Ribavirin). Except for the control group, all mice were injected intraperitoneally with 0.5 mL 105.4 50% tissue culture infectious dose (TCID50)/mL PCV2.ResultsWhile attenuating PCV2-induced downregulation of ZO-1 and occludin and restoring intestinal barrier function in a PCV2 Kunming mouse model, treatment with Matrine (40 mg/kg) attenuated ultrastructural damage and improved intestinal morphology. Mechanistically, Matrine reversed PCV2-induced autophagosome accumulation by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation and upregulating Beclin1 protein expression, thus resisting viral hijacking of enterocyte autophagy.DiscussionOur findings demonstrate that Matrine may be a novel, potential antiviral agent against PCV2 by activating intestine cellular autophagy, which provides a new strategy for host-directed drug discovery. |
| format | Article |
| id | doaj-art-dfb0b792d162492abedf76b2fda5f9a1 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-dfb0b792d162492abedf76b2fda5f9a12024-11-11T14:56:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-11-011510.3389/fmicb.2024.14550491455049Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine modelHong Wang0Hong Wang1Na Sun2Panpan Sun3Hua Zhang4Wei Yin5Xiaozhong Zheng6Kuohai Fan7Kuohai Fan8Yaogui Sun9Hongquan Li10Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaDepartment of Sports, Shanxi Agricultural University, Taigu, Shanxi, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaCentre for Inflammation Research, Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, United KingdomShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaLaboratory Animal Center, Shanxi Agricultural University, Taigu, Shanxi, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaShanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, ChinaIntroductionPorcine circovirus type 2 (PCV2) is an important pathogen that causes diarrhea in nursery and fattening pigs, resulting in huge economic losses for commercial pig farms. Protective efficacy of vaccines is compromised by mutations in pathogens. There is an urgent need to articulate the mechanism by which PCV2 destroys the host’s intestinal mucosal barrier and to find effective therapeutic drugs. Increasing attention has been paid to the natural antiviral compounds extracted from traditional Chinese medicines. In the present study, we investigated the role of Matrine in mitigating PCV2-induced intestinal damage and enhancing autophagy as a potential therapeutic strategy in mice.MethodsA total of 40 female, specific-pathogen-free-grade Kunming mice were randomly divided into four groups with 10 mice in each group: control, PCV2 infection, Matrine treatment (40 mg/kg Matrine), and Ribavirin treatment (40 mg/kg Ribavirin). Except for the control group, all mice were injected intraperitoneally with 0.5 mL 105.4 50% tissue culture infectious dose (TCID50)/mL PCV2.ResultsWhile attenuating PCV2-induced downregulation of ZO-1 and occludin and restoring intestinal barrier function in a PCV2 Kunming mouse model, treatment with Matrine (40 mg/kg) attenuated ultrastructural damage and improved intestinal morphology. Mechanistically, Matrine reversed PCV2-induced autophagosome accumulation by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation and upregulating Beclin1 protein expression, thus resisting viral hijacking of enterocyte autophagy.DiscussionOur findings demonstrate that Matrine may be a novel, potential antiviral agent against PCV2 by activating intestine cellular autophagy, which provides a new strategy for host-directed drug discovery.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1455049/fullporcine circovirus type 2matrineantiviralmechanical barrierautophagy |
| spellingShingle | Hong Wang Hong Wang Na Sun Panpan Sun Hua Zhang Wei Yin Xiaozhong Zheng Kuohai Fan Kuohai Fan Yaogui Sun Hongquan Li Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model Frontiers in Microbiology porcine circovirus type 2 matrine antiviral mechanical barrier autophagy |
| title | Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model |
| title_full | Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model |
| title_fullStr | Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model |
| title_full_unstemmed | Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model |
| title_short | Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model |
| title_sort | matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2 infected murine model |
| topic | porcine circovirus type 2 matrine antiviral mechanical barrier autophagy |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1455049/full |
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