| Autor: |
Hong-Guang Zhang, Jing Guo, Yukang Yuan, Yibo Zuo, Jin Liu, Li Zhu, Ying Miao, Xiangjie Chen, Lincong Jin, Fan Huang, Tengfei Ren, Jiuyi He, Weifeng Shi, Zhenke Wen, Chuanwu Zhu, Hui Zheng, Chunsheng Dong, Feng Qian |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Frontiers in Microbiology, Vol 11 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1664-302X |
| DOI: |
10.3389/fmicb.2020.597972 |
| Popis: |
Nef is an accessory protein encoded by human immunodeficiency virus type-1 (HIV-1) and plays important roles in regulating HIV-1 infection and viral replication. Interestingly, HIV-1 Nef can promote degradation of numerous host proteins to disrupt cellular antiviral immune response. However, how HIV-1 Nef is degraded by host factors remains largely unexplored. Here, we identified c-Cbl as a host ubiquitin E3 ligase of HIV-1 Nef. We found that c-Cbl interacts with Nef and reduces protein levels of HIV-1 Nef. Further studies demonstrated that c-Cbl promoted Lys48-linked polyubiquitination of HIV-1 Nef, thus attenuating protein stability of HIV-1 Nef. Importantly, cellular c-Cbl ubiquitinated and degraded Nef proteins produced by HIV-1 NL4-3 virions, and ultimately attenuated HIV-1 virulence for infection of THP1 cells. This study reveals a ubiquitination and proteasome-dependent degradation mechanism of HIV-1 Nef protein, and could provide potential strategies for fighting against HIV-1. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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