PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation.
The NLRP3 inflammasome is a fundamental component of the innate immune system, yet its excessive activation is intricately associated with viral pathogenesis. Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2), belonging to the family Arteriviridae, triggers dysregulated cytokine r...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012915 |
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| _version_ | 1823856880879927296 |
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| author | Lujie Zhang Yanni Gao Haoran Zhou Xiao Liang Xiaolin Jiang Wenqin Gong Yangyang Sun Desheng Zhang Xianwei Wang Hans Nauwynck Juan Bai Ping Jiang |
| author_facet | Lujie Zhang Yanni Gao Haoran Zhou Xiao Liang Xiaolin Jiang Wenqin Gong Yangyang Sun Desheng Zhang Xianwei Wang Hans Nauwynck Juan Bai Ping Jiang |
| author_sort | Lujie Zhang |
| collection | DOAJ |
| description | The NLRP3 inflammasome is a fundamental component of the innate immune system, yet its excessive activation is intricately associated with viral pathogenesis. Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2), belonging to the family Arteriviridae, triggers dysregulated cytokine release and interstitial pneumonia, which can quickly escalate to acute respiratory distress and death. However, a mechanistic understanding of PRRSV-2 progression remains unclear. Here, we screen that PRRSV-2 nsp2 activates the NLRP3 inflammasome, thereby instigating a state of hyperinflammation. Mechanistically, PRRSV-2 nsp2 interacts with the nucleotide-binding and oligomerization (NACHT) domain of NLRP3, augmenting IKKβ recruitment to driving NLRP3 translocation to the dispersed trans-Golgi network (dTGN) for oligomerization. This process facilitates ASC polymerization, culminating in the activation of the NLRP3 inflammasome. In addition, the IKKβ-dependent NLRP3 translocation to the dTGN is pivotal for pseudorabies virus (PRV) and encephalomyocarditis virus (EMCV)-induced inflammatory responses. Collectively, these results elucidate a novel mechanism of NLRP3 inflammasome activation during PRRSV-2 infection, providing valuable insights into PRRSV-2 pathogenesis. |
| format | Article |
| id | doaj-art-1246da3b0b1b4de8a7b0ee1f696d6816 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-1246da3b0b1b4de8a7b0ee1f696d68162025-02-12T05:30:41ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101291510.1371/journal.ppat.1012915PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation.Lujie ZhangYanni GaoHaoran ZhouXiao LiangXiaolin JiangWenqin GongYangyang SunDesheng ZhangXianwei WangHans NauwynckJuan BaiPing JiangThe NLRP3 inflammasome is a fundamental component of the innate immune system, yet its excessive activation is intricately associated with viral pathogenesis. Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2), belonging to the family Arteriviridae, triggers dysregulated cytokine release and interstitial pneumonia, which can quickly escalate to acute respiratory distress and death. However, a mechanistic understanding of PRRSV-2 progression remains unclear. Here, we screen that PRRSV-2 nsp2 activates the NLRP3 inflammasome, thereby instigating a state of hyperinflammation. Mechanistically, PRRSV-2 nsp2 interacts with the nucleotide-binding and oligomerization (NACHT) domain of NLRP3, augmenting IKKβ recruitment to driving NLRP3 translocation to the dispersed trans-Golgi network (dTGN) for oligomerization. This process facilitates ASC polymerization, culminating in the activation of the NLRP3 inflammasome. In addition, the IKKβ-dependent NLRP3 translocation to the dTGN is pivotal for pseudorabies virus (PRV) and encephalomyocarditis virus (EMCV)-induced inflammatory responses. Collectively, these results elucidate a novel mechanism of NLRP3 inflammasome activation during PRRSV-2 infection, providing valuable insights into PRRSV-2 pathogenesis.https://doi.org/10.1371/journal.ppat.1012915 |
| spellingShingle | Lujie Zhang Yanni Gao Haoran Zhou Xiao Liang Xiaolin Jiang Wenqin Gong Yangyang Sun Desheng Zhang Xianwei Wang Hans Nauwynck Juan Bai Ping Jiang PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation. PLoS Pathogens |
| title | PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation. |
| title_full | PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation. |
| title_fullStr | PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation. |
| title_full_unstemmed | PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation. |
| title_short | PRRSV-2 nsp2 Ignites NLRP3 inflammasome through IKKβ-dependent dispersed trans-Golgi network translocation. |
| title_sort | prrsv 2 nsp2 ignites nlrp3 inflammasome through ikkβ dependent dispersed trans golgi network translocation |
| url | https://doi.org/10.1371/journal.ppat.1012915 |
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