RNF152 regulates prototype foamy virus replication by targeting Gag polyubiquitination and VLPs production.
TL;DR
The role of RNF152 in affecting virus replication for the first time is elucidated, providing valuable insights into the mechanisms of virus replication and demonstrating the importance of ubiquitination modification in affecting viral replication.
Abstract
Prototype foamy viruses (PFVs) are complex retroviruses that establish long-term latent infections in hosts without causing disease, positioning them as potential safe gene transfer vectors. Understanding the host proteins involved in PFV replication and their interaction mechanisms may enhance gene transfer efficiency. However, only a few cellular proteins are known to influence PFV replication. Based on the transcriptomic analysis of PFV-infected HT1080 cells, we observed a potential significance of RING finger protein 152 (RNF152) in modulating PFV replication. Overexpression of RNF152 significantly inhibits PFV replication, whereas RNF152 knockdown enhances viral replication. Mechanistically, RNF152 interacts with the Gag protein to promote its polyubiquitination at lysine 396 (K396), thereby facilitating its degradation via the ubiquitin-proteasome system. Furthermore, RNF152 reduces the size and number of PFV virus-like particles (VLPs) by inhibiting the multimerization of Gag. Collectively, our findings reveal a previously unrecognized mechanism that influences PFV infection. Additionally, we elucidate the role of RNF152 in affecting virus replication for the first time, providing valuable insights into the mechanisms of virus replication and demonstrating the importance of ubiquitination modification in affecting viral replication.