Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx
Hepatitis B virus (HBV) infection affects hepatic metabolism. Serum metabolomics studies have suggested that HBV possibly hijacks the glycerol-3-phosphate (G3P) shuttle. In this study, the two glycerol-3-phosphate dehydrogenases (GPD1 and GPD2) in the G3P shuttle were analyzed for determining their...
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| Veröffentlicht in: | Journal of virology 2023-05, Vol.97 (5), p.e0058023-e0058023 |
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| creator | Liu, Canyu Zhao, Kaitao Chen, Yingshan Yao, Yongxuan Tang, Jielin Wang, Jingjing Xu, Chonghui Yang, Qi Zheng, Yi Yuan, Yifei Sun, Hao Zhang, Yongli Zhou, Yuan Chen, Jizheng Wang, Yun Wu, Chunchen Pei, Rongjuan Chen, Xinwen |
| description | Hepatitis B virus (HBV) infection affects hepatic metabolism. Serum metabolomics studies have suggested that HBV possibly hijacks the glycerol-3-phosphate (G3P) shuttle. In this study, the two glycerol-3-phosphate dehydrogenases (GPD1 and GPD2) in the G3P shuttle were analyzed for determining their role in HBV replication and the findings revealed that GPD2 and not GPD1 inhibited HBV replication. The knockdown of GPD2 expression upregulated HBV replication, while GPD2 overexpression reduced HBV replication. Moreover, the overexpression of GPD2 significantly reduced HBV replication in hydrodynamic injection-based mouse models. Mechanistically, this inhibitory effect is related to the GPD2-mediated degradation of HBx protein by recruiting the E3 ubiquitin ligase TRIM28 and not to the alterations in G3P metabolism. In conclusion, this study revealed GPD2, a key enzyme in the G3P shuttle, as a host restriction factor in HBV replication.
The glycerol-3-phosphate (G3P) shuttle is important for the delivery of cytosolic reducing equivalents into mitochondria for oxidative phosphorylation. The study analyzed two key components of the G3P shuttle and identified GPD2 as a restriction factor in HBV replication. The findings revealed a novel mechanism of GPD2-mediated inhibition of HBV replication via the recruitment of TRIM28 for degrading HBx, and the HBx-GPD2 interaction could be another potential therapeutic target for anti-HBV drug development. |
| doi_str_mv | 10.1128/jvi.00580-23 |
| format | Article |
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The glycerol-3-phosphate (G3P) shuttle is important for the delivery of cytosolic reducing equivalents into mitochondria for oxidative phosphorylation. The study analyzed two key components of the G3P shuttle and identified GPD2 as a restriction factor in HBV replication. The findings revealed a novel mechanism of GPD2-mediated inhibition of HBV replication via the recruitment of TRIM28 for degrading HBx, and the HBx-GPD2 interaction could be another potential therapeutic target for anti-HBV drug development.</description><identifier>ISSN: 0022-538X</identifier><identifier>EISSN: 1098-5514</identifier><identifier>DOI: 10.1128/jvi.00580-23</identifier><identifier>PMID: 37166302</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Animals ; Glycerol - metabolism ; Glycerolphosphate Dehydrogenase - metabolism ; Hepatitis B - metabolism ; Hepatitis B virus - physiology ; Mice ; Mitochondria - enzymology ; Molecular and Cellular Biology ; Phosphates - metabolism ; Tripartite Motif-Containing Protein 28 - metabolism ; Viral Regulatory and Accessory Proteins - genetics ; Viral Regulatory and Accessory Proteins - metabolism ; Virus Replication ; Virus-Cell Interactions</subject><ispartof>Journal of virology, 2023-05, Vol.97 (5), p.e0058023-e0058023</ispartof><rights>Copyright © 2023 American Society for Microbiology.</rights><rights>Copyright © 2023 American Society for Microbiology. 2023 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a419t-ec45457f22afc96b150061743926373ae64ceed0e1da9bcd9880493e2d9b60963</citedby><cites>FETCH-LOGICAL-a419t-ec45457f22afc96b150061743926373ae64ceed0e1da9bcd9880493e2d9b60963</cites><orcidid>0000-0002-2201-9277 ; 0000-0002-0261-1599 ; 0000-0002-4052-8155</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10231258/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10231258/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37166302$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ou, J.-H. James</contributor><creatorcontrib>Liu, Canyu</creatorcontrib><creatorcontrib>Zhao, Kaitao</creatorcontrib><creatorcontrib>Chen, Yingshan</creatorcontrib><creatorcontrib>Yao, Yongxuan</creatorcontrib><creatorcontrib>Tang, Jielin</creatorcontrib><creatorcontrib>Wang, Jingjing</creatorcontrib><creatorcontrib>Xu, Chonghui</creatorcontrib><creatorcontrib>Yang, Qi</creatorcontrib><creatorcontrib>Zheng, Yi</creatorcontrib><creatorcontrib>Yuan, Yifei</creatorcontrib><creatorcontrib>Sun, Hao</creatorcontrib><creatorcontrib>Zhang, Yongli</creatorcontrib><creatorcontrib>Zhou, Yuan</creatorcontrib><creatorcontrib>Chen, Jizheng</creatorcontrib><creatorcontrib>Wang, Yun</creatorcontrib><creatorcontrib>Wu, Chunchen</creatorcontrib><creatorcontrib>Pei, Rongjuan</creatorcontrib><creatorcontrib>Chen, Xinwen</creatorcontrib><title>Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx</title><title>Journal of virology</title><addtitle>J Virol</addtitle><addtitle>J Virol</addtitle><description>Hepatitis B virus (HBV) infection affects hepatic metabolism. Serum metabolomics studies have suggested that HBV possibly hijacks the glycerol-3-phosphate (G3P) shuttle. In this study, the two glycerol-3-phosphate dehydrogenases (GPD1 and GPD2) in the G3P shuttle were analyzed for determining their role in HBV replication and the findings revealed that GPD2 and not GPD1 inhibited HBV replication. The knockdown of GPD2 expression upregulated HBV replication, while GPD2 overexpression reduced HBV replication. Moreover, the overexpression of GPD2 significantly reduced HBV replication in hydrodynamic injection-based mouse models. Mechanistically, this inhibitory effect is related to the GPD2-mediated degradation of HBx protein by recruiting the E3 ubiquitin ligase TRIM28 and not to the alterations in G3P metabolism. In conclusion, this study revealed GPD2, a key enzyme in the G3P shuttle, as a host restriction factor in HBV replication.
The glycerol-3-phosphate (G3P) shuttle is important for the delivery of cytosolic reducing equivalents into mitochondria for oxidative phosphorylation. The study analyzed two key components of the G3P shuttle and identified GPD2 as a restriction factor in HBV replication. The findings revealed a novel mechanism of GPD2-mediated inhibition of HBV replication via the recruitment of TRIM28 for degrading HBx, and the HBx-GPD2 interaction could be another potential therapeutic target for anti-HBV drug development.</description><subject>Animals</subject><subject>Glycerol - metabolism</subject><subject>Glycerolphosphate Dehydrogenase - metabolism</subject><subject>Hepatitis B - metabolism</subject><subject>Hepatitis B virus - physiology</subject><subject>Mice</subject><subject>Mitochondria - enzymology</subject><subject>Molecular and Cellular Biology</subject><subject>Phosphates - metabolism</subject><subject>Tripartite Motif-Containing Protein 28 - metabolism</subject><subject>Viral Regulatory and Accessory Proteins - genetics</subject><subject>Viral Regulatory and Accessory Proteins - metabolism</subject><subject>Virus Replication</subject><subject>Virus-Cell Interactions</subject><issn>0022-538X</issn><issn>1098-5514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1vEzEQxS0EomnhxhntEaS6-Dv2CZUCbaVGoKogbpZjz2YdbdbB3o3If48hpYIDp9Fofu-NZh5CLyg5o5TpN-tdPCNEaoIZf4RmlBiNpaTiMZoRwhiWXH87QselrAmhQijxFB3xOVWKEzZD0yKOyXdpCDm6vrns9x5y6jHHn7tUtp0boXkP3T7ktILBFWhuoYw5-rE0V---1m7bR-_GmIZmF10zdtDc3V4vmMYLCLHKQ9WvsgsHJrVV9uMZetK6vsDz-3qCvnz8cHdxhW8-XV5fnN9gJ6gZMXghhZy3jLnWG7WkkhBF54IbpvicO1DCAwQCNDiz9MFoTYThwIJZKmIUP0FvD77babmB4GEYs-vtNseNy3ubXLT_TobY2VXaWUoYp0zq6vDq3iGn71M93W5i8dD3boA0Fct0xYhiSlb09ID6nErJ0D7socT-isrWqOzvqCzjFX99wF3ZMLtOUx7qK_7Hvvz7jgfjPznynw4TnVo</recordid><startdate>20230531</startdate><enddate>20230531</enddate><creator>Liu, Canyu</creator><creator>Zhao, Kaitao</creator><creator>Chen, Yingshan</creator><creator>Yao, Yongxuan</creator><creator>Tang, Jielin</creator><creator>Wang, Jingjing</creator><creator>Xu, Chonghui</creator><creator>Yang, Qi</creator><creator>Zheng, Yi</creator><creator>Yuan, Yifei</creator><creator>Sun, Hao</creator><creator>Zhang, Yongli</creator><creator>Zhou, Yuan</creator><creator>Chen, Jizheng</creator><creator>Wang, Yun</creator><creator>Wu, Chunchen</creator><creator>Pei, Rongjuan</creator><creator>Chen, Xinwen</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2201-9277</orcidid><orcidid>https://orcid.org/0000-0002-0261-1599</orcidid><orcidid>https://orcid.org/0000-0002-4052-8155</orcidid></search><sort><creationdate>20230531</creationdate><title>Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx</title><author>Liu, Canyu ; Zhao, Kaitao ; Chen, Yingshan ; Yao, Yongxuan ; Tang, Jielin ; Wang, Jingjing ; Xu, Chonghui ; Yang, Qi ; Zheng, Yi ; Yuan, Yifei ; Sun, Hao ; Zhang, Yongli ; Zhou, Yuan ; Chen, Jizheng ; Wang, Yun ; Wu, Chunchen ; Pei, Rongjuan ; Chen, Xinwen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a419t-ec45457f22afc96b150061743926373ae64ceed0e1da9bcd9880493e2d9b60963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Glycerol - metabolism</topic><topic>Glycerolphosphate Dehydrogenase - metabolism</topic><topic>Hepatitis B - metabolism</topic><topic>Hepatitis B virus - physiology</topic><topic>Mice</topic><topic>Mitochondria - enzymology</topic><topic>Molecular and Cellular Biology</topic><topic>Phosphates - metabolism</topic><topic>Tripartite Motif-Containing Protein 28 - metabolism</topic><topic>Viral Regulatory and Accessory Proteins - genetics</topic><topic>Viral Regulatory and Accessory Proteins - metabolism</topic><topic>Virus Replication</topic><topic>Virus-Cell Interactions</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Canyu</creatorcontrib><creatorcontrib>Zhao, Kaitao</creatorcontrib><creatorcontrib>Chen, Yingshan</creatorcontrib><creatorcontrib>Yao, Yongxuan</creatorcontrib><creatorcontrib>Tang, Jielin</creatorcontrib><creatorcontrib>Wang, Jingjing</creatorcontrib><creatorcontrib>Xu, Chonghui</creatorcontrib><creatorcontrib>Yang, Qi</creatorcontrib><creatorcontrib>Zheng, Yi</creatorcontrib><creatorcontrib>Yuan, Yifei</creatorcontrib><creatorcontrib>Sun, Hao</creatorcontrib><creatorcontrib>Zhang, Yongli</creatorcontrib><creatorcontrib>Zhou, Yuan</creatorcontrib><creatorcontrib>Chen, Jizheng</creatorcontrib><creatorcontrib>Wang, Yun</creatorcontrib><creatorcontrib>Wu, Chunchen</creatorcontrib><creatorcontrib>Pei, Rongjuan</creatorcontrib><creatorcontrib>Chen, Xinwen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Canyu</au><au>Zhao, Kaitao</au><au>Chen, Yingshan</au><au>Yao, Yongxuan</au><au>Tang, Jielin</au><au>Wang, Jingjing</au><au>Xu, Chonghui</au><au>Yang, Qi</au><au>Zheng, Yi</au><au>Yuan, Yifei</au><au>Sun, Hao</au><au>Zhang, Yongli</au><au>Zhou, Yuan</au><au>Chen, Jizheng</au><au>Wang, Yun</au><au>Wu, Chunchen</au><au>Pei, Rongjuan</au><au>Chen, Xinwen</au><au>Ou, J.-H. James</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx</atitle><jtitle>Journal of virology</jtitle><stitle>J Virol</stitle><addtitle>J Virol</addtitle><date>2023-05-31</date><risdate>2023</risdate><volume>97</volume><issue>5</issue><spage>e0058023</spage><epage>e0058023</epage><pages>e0058023-e0058023</pages><issn>0022-538X</issn><eissn>1098-5514</eissn><abstract>Hepatitis B virus (HBV) infection affects hepatic metabolism. Serum metabolomics studies have suggested that HBV possibly hijacks the glycerol-3-phosphate (G3P) shuttle. In this study, the two glycerol-3-phosphate dehydrogenases (GPD1 and GPD2) in the G3P shuttle were analyzed for determining their role in HBV replication and the findings revealed that GPD2 and not GPD1 inhibited HBV replication. The knockdown of GPD2 expression upregulated HBV replication, while GPD2 overexpression reduced HBV replication. Moreover, the overexpression of GPD2 significantly reduced HBV replication in hydrodynamic injection-based mouse models. Mechanistically, this inhibitory effect is related to the GPD2-mediated degradation of HBx protein by recruiting the E3 ubiquitin ligase TRIM28 and not to the alterations in G3P metabolism. In conclusion, this study revealed GPD2, a key enzyme in the G3P shuttle, as a host restriction factor in HBV replication.
The glycerol-3-phosphate (G3P) shuttle is important for the delivery of cytosolic reducing equivalents into mitochondria for oxidative phosphorylation. The study analyzed two key components of the G3P shuttle and identified GPD2 as a restriction factor in HBV replication. The findings revealed a novel mechanism of GPD2-mediated inhibition of HBV replication via the recruitment of TRIM28 for degrading HBx, and the HBx-GPD2 interaction could be another potential therapeutic target for anti-HBV drug development.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>37166302</pmid><doi>10.1128/jvi.00580-23</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-2201-9277</orcidid><orcidid>https://orcid.org/0000-0002-0261-1599</orcidid><orcidid>https://orcid.org/0000-0002-4052-8155</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Glycerol - metabolism Glycerolphosphate Dehydrogenase - metabolism Hepatitis B - metabolism Hepatitis B virus - physiology Mice Mitochondria - enzymology Molecular and Cellular Biology Phosphates - metabolism Tripartite Motif-Containing Protein 28 - metabolism Viral Regulatory and Accessory Proteins - genetics Viral Regulatory and Accessory Proteins - metabolism Virus Replication Virus-Cell Interactions |
| title | Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx |
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