Insights of HIV-1 and HBV transcriptional regulation by viral transactivator Tat and HBx.

Transcriptions of nascent HIV-1 RNA from the integrated proviral DNA, and HBV RNAs from a stably formed minichromosome of cccDNA, are carried out by cellular RNA polymerase II, and strongly regulated by viral transactivation proteins Tat and HBx, respectively. Both Tat and HBx are intrinsically disordered proteins with promiscuous gene transactivation activities and regulate HIV-1 and HBV transcription by multiple, but similar mechanisms. The antiviral therapies of HIV-1 and HBV effectively suppress viral replication and enable the infection into latent states. The viral life cycles of HIV-1 and HBV differ significantly, but the core mechanisms of T-cell depletion are intertwined. Consequently, future therapeutic interventions must encompass a dual strategy of viral clearance and immune reconstitution. A functional cure would be achieved by combining checkpoint inhibitors, specific T-cell activators, and drugs targeting viral persistence.