KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.
IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role...
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| Main Authors: | , , , , , , , , |
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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.1012856 |
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| author | Xiaoqian Wang Zhenshan Liu Xue Xu Xin Wang Zizhen Ming Chengrong Liu Hang Gao Tingting Li Qiming Liang |
| author_facet | Xiaoqian Wang Zhenshan Liu Xue Xu Xin Wang Zizhen Ming Chengrong Liu Hang Gao Tingting Li Qiming Liang |
| author_sort | Xiaoqian Wang |
| collection | DOAJ |
| description | IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45. This SUMOylation event leads to the association of IKKε with PML, resulting in the disruption of PML nuclear bodies (PML NBs) and subsequent increase in lytic replication of KSHV. Notably, IKKε does not affect the total expression level of PML but facilitates the translocation of PML from the nucleus to the cytoplasm during KSHV lytic replication. Further experiments utilizing mutations on the SUMOylation sites of IKKε or inhibiting IKKε using BAY-985 showed that these actions no longer impact PML NBs and completely suppress the lytic replication of KSHV. These findings not only emphasize the essential role of IKKε in the life cycle of KSHV but also illustrate how KSHV exploits IKKε through SUMOylation modification to enhance its own replication process. |
| format | Article |
| id | doaj-art-c590513930274dcaa6b97e8c7d710366 |
| 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-c590513930274dcaa6b97e8c7d7103662025-02-05T05:30:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101285610.1371/journal.ppat.1012856KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.Xiaoqian WangZhenshan LiuXue XuXin WangZizhen MingChengrong LiuHang GaoTingting LiQiming LiangIKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45. This SUMOylation event leads to the association of IKKε with PML, resulting in the disruption of PML nuclear bodies (PML NBs) and subsequent increase in lytic replication of KSHV. Notably, IKKε does not affect the total expression level of PML but facilitates the translocation of PML from the nucleus to the cytoplasm during KSHV lytic replication. Further experiments utilizing mutations on the SUMOylation sites of IKKε or inhibiting IKKε using BAY-985 showed that these actions no longer impact PML NBs and completely suppress the lytic replication of KSHV. These findings not only emphasize the essential role of IKKε in the life cycle of KSHV but also illustrate how KSHV exploits IKKε through SUMOylation modification to enhance its own replication process.https://doi.org/10.1371/journal.ppat.1012856 |
| spellingShingle | Xiaoqian Wang Zhenshan Liu Xue Xu Xin Wang Zizhen Ming Chengrong Liu Hang Gao Tingting Li Qiming Liang KSHV hijacks the antiviral kinase IKKε to initiate lytic replication. PLoS Pathogens |
| title | KSHV hijacks the antiviral kinase IKKε to initiate lytic replication. |
| title_full | KSHV hijacks the antiviral kinase IKKε to initiate lytic replication. |
| title_fullStr | KSHV hijacks the antiviral kinase IKKε to initiate lytic replication. |
| title_full_unstemmed | KSHV hijacks the antiviral kinase IKKε to initiate lytic replication. |
| title_short | KSHV hijacks the antiviral kinase IKKε to initiate lytic replication. |
| title_sort | kshv hijacks the antiviral kinase ikkε to initiate lytic replication |
| url | https://doi.org/10.1371/journal.ppat.1012856 |
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