Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB
Abstract Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone have been identified as tumor suppressors. However, their roles in virus infection remain unclear. Here, we demonstrate that PBLD upregulates the type I interferon (IFN-I) response through activating NF-kappaB (NF-κB...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54882-y |
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| author | Peili Hou Hongchao Zhu Fengyun Chu Yan Gao Xiaonan Sun Fuzhen Zhang Xiaomeng Wang Yueyue Feng Xingyu Li Yu Liu Jun Wang Xiaoyun Wang Daniel Chang He Hongmei Wang Hongbin He |
| author_facet | Peili Hou Hongchao Zhu Fengyun Chu Yan Gao Xiaonan Sun Fuzhen Zhang Xiaomeng Wang Yueyue Feng Xingyu Li Yu Liu Jun Wang Xiaoyun Wang Daniel Chang He Hongmei Wang Hongbin He |
| author_sort | Peili Hou |
| collection | DOAJ |
| description | Abstract Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone have been identified as tumor suppressors. However, their roles in virus infection remain unclear. Here, we demonstrate that PBLD upregulates the type I interferon (IFN-I) response through activating NF-kappaB (NF-κB) signaling pathway to resist viral infection in cells and mice. Mechanistically, PBLD activates NF-κB signaling pathway during viral infection via blocking tripartite motif containing 21 (TRIM21)-mediated phosphorylated inhibitory kappa B kinase beta (IKKβ) degradation. Furthermore, we show Cedrelone inhibits viral replication by increasing the PBLD protein expression and subsequently activating NF-κB-mediated IFN-I response. Furthermore, the therapeutic potential of Cedrelone lies in its ability to enhance antiviral immunity in primary macrophages and to promote survival and reduce lung tissue damage in HSV-1-infected mice in a PBLD-dependent manner. Consequently, our findings provide a potential combination model that targets PBLD for Cedrelone antiviral drug therapy, potentially paving the way for the development of broad-spectrum antiviral agents. |
| format | Article |
| id | doaj-art-3bfbd6c408b749bfa92e6e7f71512fb9 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-3bfbd6c408b749bfa92e6e7f71512fb92025-01-12T12:31:55ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-024-54882-yPhenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸBPeili Hou0Hongchao Zhu1Fengyun Chu2Yan Gao3Xiaonan Sun4Fuzhen Zhang5Xiaomeng Wang6Yueyue Feng7Xingyu Li8Yu Liu9Jun Wang10Xiaoyun Wang11Daniel Chang He12Hongmei Wang13Hongbin He14Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityThe College of Arts and Sciences, University of North Carolina at Chapel HillRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityRuminant Diseases Research Center, College of Life Sciences, Shandong Normal UniversityAbstract Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone have been identified as tumor suppressors. However, their roles in virus infection remain unclear. Here, we demonstrate that PBLD upregulates the type I interferon (IFN-I) response through activating NF-kappaB (NF-κB) signaling pathway to resist viral infection in cells and mice. Mechanistically, PBLD activates NF-κB signaling pathway during viral infection via blocking tripartite motif containing 21 (TRIM21)-mediated phosphorylated inhibitory kappa B kinase beta (IKKβ) degradation. Furthermore, we show Cedrelone inhibits viral replication by increasing the PBLD protein expression and subsequently activating NF-κB-mediated IFN-I response. Furthermore, the therapeutic potential of Cedrelone lies in its ability to enhance antiviral immunity in primary macrophages and to promote survival and reduce lung tissue damage in HSV-1-infected mice in a PBLD-dependent manner. Consequently, our findings provide a potential combination model that targets PBLD for Cedrelone antiviral drug therapy, potentially paving the way for the development of broad-spectrum antiviral agents.https://doi.org/10.1038/s41467-024-54882-y |
| spellingShingle | Peili Hou Hongchao Zhu Fengyun Chu Yan Gao Xiaonan Sun Fuzhen Zhang Xiaomeng Wang Yueyue Feng Xingyu Li Yu Liu Jun Wang Xiaoyun Wang Daniel Chang He Hongmei Wang Hongbin He Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB Nature Communications |
| title | Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB |
| title_full | Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB |
| title_fullStr | Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB |
| title_full_unstemmed | Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB |
| title_short | Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB |
| title_sort | phenazine biosynthesis like domain containing protein pbld and cedrelone promote antiviral immune response by activating nf qb |
| url | https://doi.org/10.1038/s41467-024-54882-y |
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