The HIV-1 accessory protein Vpr induces the degradation of the anti-HIV-1 agent APOBEC3G through a VprBP-mediated proteasomal pathway

• The interaction of Vpr and A3G was predicted by computer-based screen (PRISM algorithm) and confirmed by the Co-IP approach.
• Vpr reduces the virion encapsidation of A3G to enhance HIV-1 replication.
• Vpr induces the degradation of A3G through a VprBP-mediated proteasomal pathway.
• The reduction of A3G encapsidation by Vpr was due to Vpr's degradation-inducing activity.
• The crosstalk between different HIV-1-host ubiquitin ligase complex systems presented by us highlights the importance of systematic follow-up studies.

The host anti-HIV-1 factor APOBEC3G (A3G) plays a potential role in restricting HIV-1 replication, although this antagonist can be encountered and disarmed by the Vif protein. In this paper, we report that another HIV-1 accessory protein, viral protein R (Vpr), can interact with A3G and intervene in its antiviral behavior. The interaction of Vpr and A3G was predicted by computer-based screen and confirmed by a co-immunoprecipitation (Co-IP) approach. We found that Vpr could reduce the virion encapsidation of A3G to enhance viral replication. Subsequent experiments showed that Vpr downregulated A3G through Vpr-binding protein (VprBP)-mediated proteasomal degradation, and further confirmed that the reduction of A3G encapsidation associated with Vpr was due to Vpr's degradation-inducing activity. Our findings highlight the versatility of Vpr by unveiling the hostile relationship between Vpr and A3G. In addition, the observation that A3G is targeted to the proteasomal degradation pathway by Vpr in addition to Vif implicates the existence of crosstalk between different HIV-1-host ubiquitin ligase complex systems.