Institute of Virology and AIDS Research, First Hospital, Jilin University, Changchun, Jilin, China.
School of Life Sciences, Tsinghua University, Beijing, China.
J Med Virol. 2023 Jan;95(1):e28135. doi: 10.1002/jmv.28135. Epub 2022 Sep 19.
The ongoing pandemic of severe acute respiratory coronavirus 2 (SARS-CoV-2) is causing a devastating impact on public health worldwide. However, details concerning the profound impact of SARS-CoV-2 on host cells remain elusive. Here, we investigated the effects of SARS-CoV-2-encoded viral proteins on the intracellular activity of long interspersed element 1 (L1) retrotransposons using well-established reporter systems. Several nonstructural or accessory proteins (Nsps) of SARS-CoV-2 (i.e., Nsp1, Nsp3, Nsp5, and Nsp14) significantly suppress human L1 mobility, and these viral L1 inhibitors generate a complex network that modulates L1 transposition. Specifically, Nsp1 and Nsp14 inhibit the intracellular accumulation of L1 open reading frame proteins (ORF1p), whereas Nsp3, Nsp5, and Nsp14 repress the reverse transcriptase activity of L1 ORF2p. Given recent findings concerning the roles of L1 in antiviral immune activation and host genome instability, the anti-L1 activities mediated by SARS-CoV-2-encoded inhibitors suggest that SARS-CoV-2 employs different strategies to optimize the host genetic environment.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的持续大流行正在对全球公共卫生造成毁灭性影响。然而，有关 SARS-CoV-2 对宿主细胞的深远影响的细节仍不清楚。在这里，我们使用成熟的报告系统研究了 SARS-CoV-2 编码的病毒蛋白对长散布元件 1（L1）逆转录转座子细胞内活性的影响。几种 SARS-CoV-2 的非结构或辅助蛋白（Nsp）（即 Nsp1、Nsp3、Nsp5 和 Nsp14）显著抑制了人类 L1 的迁移能力，这些病毒 L1 抑制剂产生了一个调节 L1 转座的复杂网络。具体而言，Nsp1 和 Nsp14 抑制 L1 开放阅读框蛋白（ORF1p）的细胞内积累，而 Nsp3、Nsp5 和 Nsp14 则抑制 L1 ORF2p 的逆转录酶活性。鉴于最近关于 L1 在抗病毒免疫激活和宿主基因组不稳定性中的作用的发现，SARS-CoV-2 编码的抑制剂介导的抗 L1 活性表明，SARS-CoV-2 采用不同的策略来优化宿主遗传环境。
