Institute of Virology, Philipps-University Marburg, Marburg, Germany.
Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
PLoS Pathog. 2021 Apr 19;17(4):e1009496. doi: 10.1371/journal.ppat.1009496. eCollection 2021 Apr.
LINE-1 (L1) retrotransposons are autonomous transposable elements that can affect gene expression and genome integrity. Potential consequences of exogenous viral infections for L1 activity have not been studied to date. Here, we report that hepatitis C virus (HCV) infection causes a significant increase of endogenous L1-encoded ORF1 protein (L1ORF1p) levels and translocation of L1ORF1p to HCV assembly sites at lipid droplets. HCV replication interferes with retrotransposition of engineered L1 reporter elements, which correlates with HCV RNA-induced formation of stress granules and can be partially rescued by knockdown of the stress granule protein G3BP1. Upon HCV infection, L1ORF1p localizes to stress granules, associates with HCV core in an RNA-dependent manner and translocates to lipid droplets. While HCV infection has a negative effect on L1 mobilization, L1ORF1p neither restricts nor promotes HCV infection. In summary, our data demonstrate that HCV infection causes an increase of endogenous L1 protein levels and that the observed restriction of retrotransposition of engineered L1 reporter elements is caused by sequestration of L1ORF1p in HCV-induced stress granules.
LINE-1 (L1) 反转录转座子是自主转座元件，可影响基因表达和基因组完整性。迄今为止，尚未研究外源性病毒感染对 L1 活性的潜在影响。在这里，我们报告丙型肝炎病毒 (HCV) 感染可导致内源性 L1 编码的 ORF1 蛋白 (L1ORF1p) 水平显著增加，并将 L1ORF1p 易位到脂肪滴上的 HCV 组装位点。HCV 复制会干扰工程 L1 报告元件的逆转录转座，这与 HCV RNA 诱导形成应激颗粒有关，应激颗粒蛋白 G3BP1 的敲低可部分挽救该过程。HCV 感染后，L1ORF1p 定位于应激颗粒中，以 RNA 依赖性方式与 HCV 核心结合，并易位到脂肪滴。虽然 HCV 感染对 L1 动员有负面影响，但 L1ORF1p 既不限制也不促进 HCV 感染。总之，我们的数据表明 HCV 感染可导致内源性 L1 蛋白水平增加，并且观察到工程 L1 报告元件的逆转录转座受到限制，这是由于 L1ORF1p 被 HCV 诱导的应激颗粒隔离所致。
