FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production
Foot-and-mouth disease virus (FMDV) infection causes inflammatory clinical symptoms, such as high fever and vesicular lesions, even death of animals. Interleukin-1β (IL-1β) is an inflammatory cytokine that plays an essential role in inflammatory responses against viral infection. The viruses have de...
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| Online Access: | https://www.mdpi.com/1999-4915/14/1/22 |
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| author | Sk Mohiuddin Choudhury Xusheng Ma Yuanyuan Li Xiaofeng Nian Zhikuan Luo Yonghua Ma Zixiang Zhu Fan Yang Weijun Cao Haixue Zheng |
| author_facet | Sk Mohiuddin Choudhury Xusheng Ma Yuanyuan Li Xiaofeng Nian Zhikuan Luo Yonghua Ma Zixiang Zhu Fan Yang Weijun Cao Haixue Zheng |
| author_sort | Sk Mohiuddin Choudhury |
| collection | DOAJ |
| description | Foot-and-mouth disease virus (FMDV) infection causes inflammatory clinical symptoms, such as high fever and vesicular lesions, even death of animals. Interleukin-1β (IL-1β) is an inflammatory cytokine that plays an essential role in inflammatory responses against viral infection. The viruses have developed multiple strategies to induce the inflammatory responses, including regulation of IL-1β production. However, the molecular mechanism underlying the induction of IL-1β by FMDV remains not fully understood. Here, we found that FMDV robustly induced IL-1β production in macrophages and pigs. Infection of Casp-1 inhibitor-treated cells and NOD-, LRR- and pyrin domain-containing 3 (NLRP3)-knockdown cells indicated that NLRP3 is essential for FMDV-induced IL-1β secretion. More importantly, we found that FMDV L<sup>pro</sup> associates with the NACHT and LRR domains of NLRP3 to promote NLRP3 inflammasome assembly and IL-1β secretion. Moreover, FMDV L<sup>pro</sup> induces calcium influx and potassium efflux, which trigger NLRP3 activation. Our data revealed the mechanism underlying the activation of the NLRP3 inflammasome after FMDV L<sup>pro</sup> expression, thus providing insights for the control of FMDV infection-induced inflammation. |
| first_indexed | 2024-03-10T00:21:54Z |
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| id | doaj.art-7adb0f95aca54d489e6c569d3a3490aa |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T00:21:54Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-7adb0f95aca54d489e6c569d3a3490aa2023-11-23T15:40:55ZengMDPI AGViruses1999-49152021-12-011412210.3390/v14010022FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β ProductionSk Mohiuddin Choudhury0Xusheng Ma1Yuanyuan Li2Xiaofeng Nian3Zhikuan Luo4Yonghua Ma5Zixiang Zhu6Fan Yang7Weijun Cao8Haixue Zheng9State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaDepartment of Animal Medicine, Gansu Agricultural University, Lanzhou 730070, ChinaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaDepartment of Animal Medicine, Gansu Agricultural University, Lanzhou 730070, ChinaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, ChinaFoot-and-mouth disease virus (FMDV) infection causes inflammatory clinical symptoms, such as high fever and vesicular lesions, even death of animals. Interleukin-1β (IL-1β) is an inflammatory cytokine that plays an essential role in inflammatory responses against viral infection. The viruses have developed multiple strategies to induce the inflammatory responses, including regulation of IL-1β production. However, the molecular mechanism underlying the induction of IL-1β by FMDV remains not fully understood. Here, we found that FMDV robustly induced IL-1β production in macrophages and pigs. Infection of Casp-1 inhibitor-treated cells and NOD-, LRR- and pyrin domain-containing 3 (NLRP3)-knockdown cells indicated that NLRP3 is essential for FMDV-induced IL-1β secretion. More importantly, we found that FMDV L<sup>pro</sup> associates with the NACHT and LRR domains of NLRP3 to promote NLRP3 inflammasome assembly and IL-1β secretion. Moreover, FMDV L<sup>pro</sup> induces calcium influx and potassium efflux, which trigger NLRP3 activation. Our data revealed the mechanism underlying the activation of the NLRP3 inflammasome after FMDV L<sup>pro</sup> expression, thus providing insights for the control of FMDV infection-induced inflammation.https://www.mdpi.com/1999-4915/14/1/22foot-and-mouth disease virusinflammationNLRP3leader proteinNF-κBion channel |
| spellingShingle | Sk Mohiuddin Choudhury Xusheng Ma Yuanyuan Li Xiaofeng Nian Zhikuan Luo Yonghua Ma Zixiang Zhu Fan Yang Weijun Cao Haixue Zheng FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production Viruses foot-and-mouth disease virus inflammation NLRP3 leader protein NF-κB ion channel |
| title | FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production |
| title_full | FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production |
| title_fullStr | FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production |
| title_full_unstemmed | FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production |
| title_short | FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production |
| title_sort | fmdv leader protein interacts with the nacht and lrr domains of nlrp3 to promote il 1β production |
| topic | foot-and-mouth disease virus inflammation NLRP3 leader protein NF-κB ion channel |
| url | https://www.mdpi.com/1999-4915/14/1/22 |
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