Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.
J Med Virol. 2023 Dec;95(12):e29294. doi: 10.1002/jmv.29294.
Around 99% of cervical cancer and 5%-10% of human cancer are associated with human papillomaviruses (HPV). Notably, the life-cycle of HPV begins by low-level infection of the basal cells of the stratified epithelium, where the viral genomes are replicated and passed on to the daughter proliferating basal cells. The production of new viral particles remains restricted to eventually differentiated cells. HPVs support their persistent infectious cycle by hijacking pivotal pathways and cellular processes. Bromodomain-containing protein 4 (BRD4) is one of the essential cellular factors involved in multiple stages of viral transcription and replication. In this review, we demonstrate the role of BRD4 in the multiple stages of HPV infectious cycle. Also, we provide an overview of the intense research about the cellular functions of BRD4, the mechanism of action of bromodomain and extra terminal inhibitors, and how it could lead to the development of antiviral/anticancer therapies.
约 99%的宫颈癌和 5%-10%的人类癌症与人类乳头瘤病毒（HPV）有关。值得注意的是，HPV 的生命周期始于复层上皮的基底层的低度感染，病毒基因组在此处复制并传递给增殖的子基底层细胞。新的病毒颗粒的产生仍然局限于最终分化的细胞。HPV 通过劫持关键途径和细胞过程来支持其持续的感染周期。含有溴结构域的蛋白 4（BRD4）是参与病毒转录和复制多个阶段的必需细胞因子之一。在这篇综述中，我们展示了 BRD4 在 HPV 感染周期的多个阶段中的作用。此外，我们还概述了关于 BRD4 的细胞功能、溴结构域和末端外抑制剂的作用机制的大量研究，以及它如何导致抗病毒/抗癌疗法的发展。
