Wu Zhonglan, Pei Jianxin, Li Yong
College of Life Sciences, University of Ningxia, Wencui Street, Yinchuan, Ningxia, China.
Ningxia Center for Disease Control and Prevention, 528, Shengli Street, Yinchuan, Ningxia, China.
Virus Genes. 2025 Aug 12. doi: 10.1007/s11262-025-02176-w.
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.
整合的前病毒DNA转录产生的新生HIV-1 RNA，以及cccDNA稳定形成的微型染色体转录产生的HBV RNA，均由细胞RNA聚合酶II进行转录，并分别受到病毒反式激活蛋白Tat和HBx的强烈调控。Tat和HBx都是具有混杂基因反式激活活性的内在无序蛋白，它们通过多种但相似的机制调节HIV-1和HBV转录。HIV-1和HBV的抗病毒疗法可有效抑制病毒复制，并使感染进入潜伏状态。HIV-1和HBV的病毒生命周期差异显著，但T细胞耗竭的核心机制相互交织。因此，未来的治疗干预必须包括病毒清除和免疫重建的双重策略。通过联合检查点抑制剂、特异性T细胞激活剂和靶向病毒持续性的药物，有望实现功能性治愈。
