USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication
- Sun Yat-sen University, China
- Guangzhou Eighth People's Hospital, China
Abstract
The antiviral activity of host factor apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) and its degradation mediated by human immunodeficiency virus type 1 (HIV-1) Vif protein are important topics. Although accumulating evidence indicates the importance of deubiquitination enzymes (DUBs) in innate immunity, it is unknown if they participate in A3G stability. Here, we found that USP49 directly interacts with A3G and efficiently removes ubiquitin, consequently increasing A3G protein expression and significantly enhancing its anti-HIV-1 activity. Unexpectedly, A3G degradation was also mediated by a Vif- and cullin-ring-independent pathway, which was effectively counteracted by USP49. Furthermore, clinical data suggested that USP49 is correlated with A3G protein expression and hypermutations in Vif-positive proviruses, and inversely with the intact provirus ratio in the HIV-1 latent reservoir. Our studies demonstrated a mechanism to effectively stabilize A3G expression, which could comprise a target to control HIV-1 infection and eradicate the latent reservoir.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
National Special Research Program of China for Important Infectious Diseases (2018ZX10302103; 2017ZX10202102)
- Hui Zhang
The Important Key Program of the Natural Science Foundation of China (81730060)
- Hui Zhang
The International Collaboration Program of the Natural Science Foundation of China and the U.S. NIH (81561128007)
- Hui Zhang
The Joint-Innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou (201803040002)
- Hui Zhang
The Science and Technology Planning Project of Guangzhou (201704020226)
- Ting Pan
Pearl River S and T Nova Program of Guangzhou (201806010118)
- Ting Pan
National Natural Science Foundation of China (8197080527)
- Ting Pan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All human samples were anonymously coded in accordance with the local ethical guidelines (as stipulated by the Declaration of Helsinki). The Ethics Review Board of Sun Yat-Sen University and the Ethics Review Board of Guangzhou 8th People's Hospital approved this study.Written informed consents were provided by all study participants, and the protocol was approved by the IRB of Guangzhou Eighth People's Hospital (Guangzhou, China).
Copyright
© 2019, Pan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication
eLife 8:e48318.
https://doi.org/10.7554/eLife.48318
