Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation
Various lipid metabolism-related factors are essential for Zika virus (ZIKV) replication. In this study, we revealed a crucial role of diacylglycerol O-acyltransferase 2 (DGAT2) in ZIKV replication using a short hairpin RNA-based gene knockdown technique. The replication of ZIKV was significantly in...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2024-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0511 |
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| author | Xiaotong Luo Yunxiang Yuan Xiaocao Ma Xin Luo Jiannan Chen Cancan Chen Xiaoyi Yang Jinna Yang Xuanfeng Zhu Meiyu Li Yang Liu Ping Zhang Chao Liu |
| author_facet | Xiaotong Luo Yunxiang Yuan Xiaocao Ma Xin Luo Jiannan Chen Cancan Chen Xiaoyi Yang Jinna Yang Xuanfeng Zhu Meiyu Li Yang Liu Ping Zhang Chao Liu |
| author_sort | Xiaotong Luo |
| collection | DOAJ |
| description | Various lipid metabolism-related factors are essential for Zika virus (ZIKV) replication. In this study, we revealed a crucial role of diacylglycerol O-acyltransferase 2 (DGAT2) in ZIKV replication using a short hairpin RNA-based gene knockdown technique. The replication of ZIKV was significantly inhibited by DGAT2 depletion in multiple cell lines and restored by trans-complementation with DGAT2. Mechanistically, DGAT2 is recruited in the viral replication complex by interacting with non-structural (NS) proteins. Among them, both human and murine DGAT2s can be cleaved by NS2B3 at the 122R-R-S124 site. Interestingly, the cleavage product of DGAT2 becomes more stable and is sufficient to promote the lipid droplet (LD) formation independent of its enzymatic activity. This work identifies DGAT2 as a novel target of the viral protease NS2B3 and elucidates that DGAT2 is recruited by viral proteins into the replication complex, thereby playing a proviral role by promoting LD formation, which advances our understanding of host–flavivirus interaction. |
| format | Article |
| id | doaj-art-a2ecdfeda18b4c15848fcf1cec16e486 |
| institution | OA Journals |
| issn | 2639-5274 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-a2ecdfeda18b4c15848fcf1cec16e4862025-08-20T02:11:30ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742024-01-01710.34133/research.0511Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet FormationXiaotong Luo0Yunxiang Yuan1Xiaocao Ma2Xin Luo3Jiannan Chen4Cancan Chen5Xiaoyi Yang6Jinna Yang7Xuanfeng Zhu8Meiyu Li9Yang Liu10Ping Zhang11Chao Liu12Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.Various lipid metabolism-related factors are essential for Zika virus (ZIKV) replication. In this study, we revealed a crucial role of diacylglycerol O-acyltransferase 2 (DGAT2) in ZIKV replication using a short hairpin RNA-based gene knockdown technique. The replication of ZIKV was significantly inhibited by DGAT2 depletion in multiple cell lines and restored by trans-complementation with DGAT2. Mechanistically, DGAT2 is recruited in the viral replication complex by interacting with non-structural (NS) proteins. Among them, both human and murine DGAT2s can be cleaved by NS2B3 at the 122R-R-S124 site. Interestingly, the cleavage product of DGAT2 becomes more stable and is sufficient to promote the lipid droplet (LD) formation independent of its enzymatic activity. This work identifies DGAT2 as a novel target of the viral protease NS2B3 and elucidates that DGAT2 is recruited by viral proteins into the replication complex, thereby playing a proviral role by promoting LD formation, which advances our understanding of host–flavivirus interaction.https://spj.science.org/doi/10.34133/research.0511 |
| spellingShingle | Xiaotong Luo Yunxiang Yuan Xiaocao Ma Xin Luo Jiannan Chen Cancan Chen Xiaoyi Yang Jinna Yang Xuanfeng Zhu Meiyu Li Yang Liu Ping Zhang Chao Liu Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation Research |
| title | Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation |
| title_full | Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation |
| title_fullStr | Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation |
| title_full_unstemmed | Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation |
| title_short | Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation |
| title_sort | diacylglycerol o acyltransferase 2 a novel target of flavivirus ns2b3 protease promotes zika virus replication by regulating lipid droplet formation |
| url | https://spj.science.org/doi/10.34133/research.0511 |
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