TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination
Rabies, a highly fatal zoonotic disease, is a significant global public health threat. Currently, the pathogenic mechanism of rabies has not been fully elucidated, and no effective treatment for rabies is available. Increasing evidence shows that the tripartite-motif protein (TRIM) family of protein...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10892 |
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| author | Boyue Zhang Ting Cai Hongling He Xuezhe Huang Guie Chen Yanqin Lai Yongwen Luo Shile Huang Jun Luo Xiaofeng Guo |
| author_facet | Boyue Zhang Ting Cai Hongling He Xuezhe Huang Guie Chen Yanqin Lai Yongwen Luo Shile Huang Jun Luo Xiaofeng Guo |
| author_sort | Boyue Zhang |
| collection | DOAJ |
| description | Rabies, a highly fatal zoonotic disease, is a significant global public health threat. Currently, the pathogenic mechanism of rabies has not been fully elucidated, and no effective treatment for rabies is available. Increasing evidence shows that the tripartite-motif protein (TRIM) family of proteins participates in the host’s regulation of viral replication. Studies have demonstrated the upregulated expression of tripartite-motif protein 21 (TRIM21) in the brain tissue of mice infected with the rabies virus. Related studies have shown that TRIM21 knockdown inhibits RABV replication, while overexpression of TRIM21 exerted the opposite effect. Knockdown of interferon-alpha and interferon-beta modulates the inhibition of RABV replication caused by TRIM21 knockdown and promotes the replication of the virus. Furthermore, our previous study revealed that TRIM21 regulates the secretion of type I interferon during RABV infection by targeting interferon regulatory factor 7 (IRF7). IRF7 knockdown reduced the inhibition of RABV replication caused by the knockdown of TRIM21 and promoted viral replication. TRIM21 regulates RABV replication via the IRF7-IFN axis. Our study identified TRIM21 as a novel host factor required by RABV for replication. Thus, TRIM21 is a potential target for rabies treatment or management. |
| first_indexed | 2024-03-11T01:39:03Z |
| format | Article |
| id | doaj.art-5d274a7d09674e8281ac4a9218c30b2e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:39:03Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5d274a7d09674e8281ac4a9218c30b2e2023-11-18T16:45:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131089210.3390/ijms241310892TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through UbiquitinationBoyue Zhang0Ting Cai1Hongling He2Xuezhe Huang3Guie Chen4Yanqin Lai5Yongwen Luo6Shile Huang7Jun Luo8Xiaofeng Guo9College of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USACollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510000, ChinaRabies, a highly fatal zoonotic disease, is a significant global public health threat. Currently, the pathogenic mechanism of rabies has not been fully elucidated, and no effective treatment for rabies is available. Increasing evidence shows that the tripartite-motif protein (TRIM) family of proteins participates in the host’s regulation of viral replication. Studies have demonstrated the upregulated expression of tripartite-motif protein 21 (TRIM21) in the brain tissue of mice infected with the rabies virus. Related studies have shown that TRIM21 knockdown inhibits RABV replication, while overexpression of TRIM21 exerted the opposite effect. Knockdown of interferon-alpha and interferon-beta modulates the inhibition of RABV replication caused by TRIM21 knockdown and promotes the replication of the virus. Furthermore, our previous study revealed that TRIM21 regulates the secretion of type I interferon during RABV infection by targeting interferon regulatory factor 7 (IRF7). IRF7 knockdown reduced the inhibition of RABV replication caused by the knockdown of TRIM21 and promoted viral replication. TRIM21 regulates RABV replication via the IRF7-IFN axis. Our study identified TRIM21 as a novel host factor required by RABV for replication. Thus, TRIM21 is a potential target for rabies treatment or management.https://www.mdpi.com/1422-0067/24/13/10892rabies virusinterferonIRF7TRIM21ubiquitination |
| spellingShingle | Boyue Zhang Ting Cai Hongling He Xuezhe Huang Guie Chen Yanqin Lai Yongwen Luo Shile Huang Jun Luo Xiaofeng Guo TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination International Journal of Molecular Sciences rabies virus interferon IRF7 TRIM21 ubiquitination |
| title | TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination |
| title_full | TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination |
| title_fullStr | TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination |
| title_full_unstemmed | TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination |
| title_short | TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination |
| title_sort | trim21 promotes rabies virus production by degrading irf7 through ubiquitination |
| topic | rabies virus interferon IRF7 TRIM21 ubiquitination |
| url | https://www.mdpi.com/1422-0067/24/13/10892 |
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