TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein
Abstract Chronic hepatitis B virus (HBV) infection is a major medical concern worldwide. Current treatments for HBV infection effectively inhibit virus replication; however, these treatments cannot cure HBV and novel treatment-strategies should be necessary. In this study, we identified tripartite m...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40688-3 |
| _version_ | 1797452817638621184 |
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| author | Yuki Nakaya Tsutomu Nishizawa Hironori Nishitsuji Hiromi Morita Tomoko Yamagata Daichi Onomura Kazumoto Murata |
| author_facet | Yuki Nakaya Tsutomu Nishizawa Hironori Nishitsuji Hiromi Morita Tomoko Yamagata Daichi Onomura Kazumoto Murata |
| author_sort | Yuki Nakaya |
| collection | DOAJ |
| description | Abstract Chronic hepatitis B virus (HBV) infection is a major medical concern worldwide. Current treatments for HBV infection effectively inhibit virus replication; however, these treatments cannot cure HBV and novel treatment-strategies should be necessary. In this study, we identified tripartite motif-containing protein 26 (TRIM26) could be a supportive factor for HBV replication. Small interfering RNA-mediated TRIM26 knockdown (KD) modestly attenuated HBV replication in human hepatocytes. Endogenous TRIM26 physically interacted with HBV core protein (HBc), but not polymerase and HBx, through the TRIM26 SPRY domain. Unexpectedly, TRIM26 inhibited HBc ubiquitination even though TRIM26 is an E3 ligase. HBc was degraded by TRIM26 KD in Huh-7 cells, whereas the reduction was restored by a proteasome inhibitor. RING domain-deleted TRIM26 mutant (TRIM26ΔR), a dominant negative form of TRIM26, sequestered TRIM26 from HBc, resulting in promoting HBc degradation. Taking together, this study demonstrated that HBV utilizes TRIM26 to avoid the proteasome-dependent HBc degradation. The interaction between TRIM26 and HBc might be a novel therapeutic target against HBV infection. |
| first_indexed | 2024-03-09T15:14:09Z |
| format | Article |
| id | doaj.art-dbbf4ec4360340d3843f199fe975ab0e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:14:09Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dbbf4ec4360340d3843f199fe975ab0e2023-11-26T13:13:35ZengNature PortfolioScientific Reports2045-23222023-08-0113111310.1038/s41598-023-40688-3TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core proteinYuki Nakaya0Tsutomu Nishizawa1Hironori Nishitsuji2Hiromi Morita3Tomoko Yamagata4Daichi Onomura5Kazumoto Murata6Division of Virology, Department of Infection and Immunity, Jichi Medical UniversityDivision of Virology, Department of Infection and Immunity, Jichi Medical UniversityDepartment of Virology and Parasitology, School of Medicine, Fujita Health UniversityDivision of Virology, Department of Infection and Immunity, Jichi Medical UniversityDivision of Virology, Department of Infection and Immunity, Jichi Medical UniversityDivision of Virology, Department of Infection and Immunity, Jichi Medical UniversityDivision of Virology, Department of Infection and Immunity, Jichi Medical UniversityAbstract Chronic hepatitis B virus (HBV) infection is a major medical concern worldwide. Current treatments for HBV infection effectively inhibit virus replication; however, these treatments cannot cure HBV and novel treatment-strategies should be necessary. In this study, we identified tripartite motif-containing protein 26 (TRIM26) could be a supportive factor for HBV replication. Small interfering RNA-mediated TRIM26 knockdown (KD) modestly attenuated HBV replication in human hepatocytes. Endogenous TRIM26 physically interacted with HBV core protein (HBc), but not polymerase and HBx, through the TRIM26 SPRY domain. Unexpectedly, TRIM26 inhibited HBc ubiquitination even though TRIM26 is an E3 ligase. HBc was degraded by TRIM26 KD in Huh-7 cells, whereas the reduction was restored by a proteasome inhibitor. RING domain-deleted TRIM26 mutant (TRIM26ΔR), a dominant negative form of TRIM26, sequestered TRIM26 from HBc, resulting in promoting HBc degradation. Taking together, this study demonstrated that HBV utilizes TRIM26 to avoid the proteasome-dependent HBc degradation. The interaction between TRIM26 and HBc might be a novel therapeutic target against HBV infection.https://doi.org/10.1038/s41598-023-40688-3 |
| spellingShingle | Yuki Nakaya Tsutomu Nishizawa Hironori Nishitsuji Hiromi Morita Tomoko Yamagata Daichi Onomura Kazumoto Murata TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein Scientific Reports |
| title | TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein |
| title_full | TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein |
| title_fullStr | TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein |
| title_full_unstemmed | TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein |
| title_short | TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein |
| title_sort | trim26 positively affects hepatitis b virus replication by inhibiting proteasome dependent degradation of viral core protein |
| url | https://doi.org/10.1038/s41598-023-40688-3 |
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