Virginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA.
Virginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA; VCU Massey Cancer Center, Richmond, Virginia, USA.
Virology. 2022 Oct;575:54-62. doi: 10.1016/j.virol.2022.08.007. Epub 2022 Aug 27.
Following infection by HPV16, the viral proteins E1 and E2 induce viral genome replication in association with host factors. Here we demonstrate that E2 also plays a role in promoting short-term cellular proliferation in the presence of an active DDR. Cisplatin treatment of E2 expressing cells results in short-term proliferation likely due to a block of cellular senescence and apoptosis. However, long-term growth of E2 expressing cells following cisplatin treatment is attenuated due to an accumulation of DNA damage. We discuss a possible role for this E2 function during the viral life cycle. It is also notable that E2 expressing HPV16 positive cancers have a better clinical outcome than non-E2 expressing tumors. While there are a variety of reasons for the better outcome of patients with E2 expressing tumors, this report suggests that E2 regulation of the DNA damage response may be a contributory factor.
HPV16 感染后，病毒蛋白 E1 和 E2 与宿主因子一起诱导病毒基因组复制。在这里，我们证明 E2 也在 DDR 活跃的情况下促进短期细胞增殖中发挥作用。顺铂处理表达 E2 的细胞会导致短期增殖，这可能是由于细胞衰老和凋亡被阻断。然而，由于 DNA 损伤的积累，表达 E2 的细胞在顺铂处理后长期生长受到抑制。我们讨论了这种 E2 功能在病毒生命周期中的可能作用。值得注意的是，表达 E2 的 HPV16 阳性癌症的临床预后要好于非表达 E2 的肿瘤。虽然 E2 表达肿瘤患者预后较好的原因有很多，但本报告表明，E2 对 DNA 损伤反应的调节可能是一个促成因素。
