Frontiers in Microbiology (Nov 2020)
Ubiquitin E3 Ligase c-Cbl Is a Host Negative Regulator of Nef Protein of HIV-1
- Hong-Guang Zhang,
- Hong-Guang Zhang,
- Jing Guo,
- Jing Guo,
- Yukang Yuan,
- Yukang Yuan,
- Yibo Zuo,
- Yibo Zuo,
- Jin Liu,
- Li Zhu,
- Ying Miao,
- Ying Miao,
- Xiangjie Chen,
- Xiangjie Chen,
- Lincong Jin,
- Lincong Jin,
- Fan Huang,
- Fan Huang,
- Tengfei Ren,
- Tengfei Ren,
- Jiuyi He,
- Jiuyi He,
- Weifeng Shi,
- Zhenke Wen,
- Chuanwu Zhu,
- Hui Zheng,
- Hui Zheng,
- Chunsheng Dong,
- Chunsheng Dong,
- Feng Qian
Affiliations
- Hong-Guang Zhang
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Hong-Guang Zhang
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Jing Guo
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Jing Guo
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Yukang Yuan
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Yukang Yuan
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Yibo Zuo
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Yibo Zuo
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Jin Liu
- The Second Affiliated Hospital of Soochow University, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China
- Li Zhu
- The Second Affiliated Hospital of Soochow University, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China
- Ying Miao
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Ying Miao
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Xiangjie Chen
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Xiangjie Chen
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Lincong Jin
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Lincong Jin
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Fan Huang
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Fan Huang
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Tengfei Ren
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Tengfei Ren
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Jiuyi He
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Jiuyi He
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Weifeng Shi
- Department of Laboratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
- Zhenke Wen
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Chuanwu Zhu
- The Second Affiliated Hospital of Soochow University, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China
- Hui Zheng
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Hui Zheng
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Chunsheng Dong
- Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
- Chunsheng Dong
- Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China
- Feng Qian
- The Second Affiliated Hospital of Soochow University, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China
- DOI
- https://doi.org/10.3389/fmicb.2020.597972
- Journal volume & issue
-
Vol. 11
Abstract
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.
Keywords
