Li Yan, Shen Siyu, Guo Haoran, Zhang Zhe, Zhang Lili, Yang Qingran, Gao Yanhang, Niu Junqi, Wei Wei
Institute of Virology and AIDS Research, First Hospital, Jilin University, Changchun, China.
Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Translational Medicine, First Hospital, Jilin University, Changchun, China.
Front Microbiol. 2021 Oct 18;12:706241. doi: 10.3389/fmicb.2021.706241. eCollection 2021.
Long interspersed element 1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome that can serve as an endogenous upstream activator of cytoplasmic nucleic acid sensing pathways to elicit an antiviral immune response. In this study, we investigated the influence of enteroviral infection on L1 mobility. The results showed that infection with different enteroviruses, both EV-D68 and EV-A71, blocked L1 transposition. We screened diverse viral accessory proteins for L1 activity and identified EV-D68 2A, 3A, 3C, and EV-A71 ORF2p proteins as viral L1 inhibitors. EV-D68 2A suppressed L1 mobility by expression suppression of L1 proteins. Viral proteins 3A and 3C restricted ORF2p-mediated L1 reverse transcription in isolated L1 ribonucleoproteins. The newly identified enteroviral protein ORF2p inhibited the expression of L1 ORF1p. Altogether, our findings shed light on the strict modulation of L1 retrotransposons during enterovirus replication.
长散在核元件1（LINE-1或L1）是人类基因组中唯一活跃的自主逆转录转座子，可作为细胞质核酸传感途径的内源性上游激活剂，引发抗病毒免疫反应。在本研究中，我们调查了肠道病毒感染对L1移动性的影响。结果表明，感染不同的肠道病毒，包括EV-D68和EV-A71，均会阻断L1转座。我们筛选了多种病毒辅助蛋白以检测其对L1活性的影响，并鉴定出EV-D68 2A、3A、3C以及EV-A71 ORF2p蛋白为病毒L1抑制剂。EV-D68 2A通过抑制L1蛋白的表达来抑制L1移动性。病毒蛋白3A和3C在分离的L1核糖核蛋白中限制ORF2p介导的L1逆转录。新鉴定出的肠道病毒蛋白ORF2p抑制L1 ORF1p的表达。总之，我们的研究结果揭示了肠道病毒复制过程中对L1逆转录转座子的严格调控。
