Our findings reveal that TA not only robustly reactivates latent HIV-1 but also targets the PRC1 complex by promoting the interaction between CBX4 and CUL4A, leading to CBX4 degradation and subsequent increase in HIV-1 transcription.(Fig. 7) This mechanism results in the reduction of H3K27me3 in the HIV-1 LTR region, a significant epigenetic change that aids in reactivating latent infections. Here, CUL4A is linked to disease arising from reactivation of latent virus.