Department of Laboratory Medicine, Lund University, 221 84 Lund, Sweden.
Department of Laboratory Medicine, Lund University, 221 84 Lund, Sweden.
Virology. 2018 Aug;521:1-19. doi: 10.1016/j.virol.2018.05.019. Epub 2018 Jun 1.
Adenosine plays an important role in cell death and differentiation as well as in tumorigenesis and the intra- and extra-cellular levels range from nanomolar to millimolar levels under various physiological or pathophysiological conditions. Here we report that adenosine can activate HPV16 late gene expression in a dose- and time-dependent manner, but only in the presence of guanosine. This activation occurred within hours after addition of the nucleosides and was primarily dependent on the ENT1 nucleoside transporter protein. Induction of HPV16 late gene expression was mainly the result of increased read-through at the early HPV16 polyadenylation signal into the late region of the HPV16 genome, thereby producing HPV16 late L2 mRNAs. The effect of guanosine and adenosine on HPV16 late gene expression was mediated by the increased binding to HPV16 mRNAs and nuclear export of the cellular HuR protein. Our results demonstrate that nucleosides can affect HPV16 gene expression.
腺苷在细胞死亡和分化以及肿瘤发生中起着重要作用，并且在各种生理或病理生理条件下，细胞内和细胞外的水平范围从纳摩尔到毫摩尔。在这里，我们报告说，腺苷可以以剂量和时间依赖的方式激活 HPV16 晚期基因表达，但仅在存在鸟苷的情况下。这种激活发生在添加核苷后的数小时内，主要依赖于 ENT1 核苷转运蛋白。HPV16 晚期基因表达的诱导主要是由于在早期 HPV16 多聚腺苷酸化信号进入 HPV16 基因组的晚期区域时增加了通读，从而产生 HPV16 晚期 L2 mRNAs。鸟苷和腺苷对 HPV16 晚期基因表达的影响是通过增加 HPV16 mRNA 的结合和细胞 HuR 蛋白的核输出来介导的。我们的结果表明，核苷可以影响 HPV16 基因表达。
