Filovirus Laboratory, INSERM U758, Human Virology Department, Université de Lyon, Claude Bernard Université Lyon-1, Ecole Normale Supérieure de Lyon, France.
J Infect Dis. 2011 Nov;204 Suppl 3:S941-6. doi: 10.1093/infdis/jir321.
Synthesis of the structural, surface glycoprotein (GP) of Ebola virus (EBOV) is dependent on transcriptional RNA editing phenomenon. Editing results in the insertion of an extra adenosine by viral polymerase at the editing site (7 consecutive template uridines) during transcription of GP gene of the wild-type virus (EBOV/7U). In this study, we demonstrate that passage of EBOV/7U in Vero E6 cells results in the appearance and rapid accumulation of a variant (EBOV/8U) containing an additional uridine at the editing site in the viral genome. EBOV/8U outgrows and eventually replaces the wild-type EBOV during 4-5 passages. On the contrary, infection of guinea pigs with EBOV/8U leads to the appearance and rapid predominance by EBOV/7U. These rapid conversions suggest that editing of the genomic RNA occurs at a higher frequency than previously thought. In addition, it indicates that the EBOV/7U phenotype has a selective advantage that is linked to controlled expression of GP and/or expression of secreted sGP, the primary gene product for wild-type EBOV. This study demonstrates the potential for insertion and deletion of uridines in the editing site of the EBOV genomic RNA, depending on environmental constraints.
埃博拉病毒（EBOV）结构和表面糖蛋白（GP）的合成依赖于转录 RNA 编辑现象。在野生型病毒（EBOV/7U）GP 基因的转录过程中，聚合酶在编辑位点（7 个连续的模板尿嘧啶）插入一个额外的腺嘌呤，从而导致编辑结果。在本研究中，我们证明，EBOV/7U 在 Vero E6 细胞中的传代导致在病毒基因组中编辑位点出现并迅速积累一个额外尿嘧啶的变体（EBOV/8U）。EBOV/8U 在 4-5 次传代中生长并最终取代野生型 EBOV。相反，用 EBOV/8U 感染豚鼠会导致 EBOV/7U 的出现和迅速占主导地位。这些快速转换表明，基因组 RNA 的编辑发生频率高于先前的想象。此外，这表明 EBOV/7U 表型具有选择优势，与 GP 的控制表达和/或野生型 EBOV 的主要基因产物分泌 sGP 的表达有关。本研究表明，EBOV 基因组 RNA 的编辑位点可能会根据环境限制插入和删除尿嘧啶。
