Genomic RNA Editing and Its Impact on Ebola Virus Adaptation During Serial Passages in Cell Culture and Infection of Guinea Pigs
Genomic RNA Editing and Its Impact on Ebola Virus Adaptation During Serial Passages in Cell Culture and Infection of Guinea Pigs
复制标题
DOI：
10.1093/infdis/jir321
复制
发表时间：
2011-11-01
影响因子：
6.4
通讯作者：
Volchkov, Viktor E.
中科院分区：
文献类型：
--
作者：
Volchkova, Valentina A.;Dolnik, Olga;Volchkov, Viktor E.
埃博拉病毒（EBOV）的结构性表面糖蛋白（GP）的合成依赖于转录RNA编辑现象。编辑导致在野生型病毒（EBOV/7 U）的GP基因的转录期间通过病毒聚合酶在编辑位点（7个连续的模板尿苷）处插入额外的腺苷。在这项研究中，我们证明了EBOV/7 U在Vero E6细胞中的传代导致在病毒基因组中的编辑位点处含有额外尿苷的变体（EBOV/8 U）的出现和快速积累。EBOV/8 U在4-5代期间生长超过并最终取代野生型EBOV。相反，用EBOV/8 U感染豚鼠导致EBOV/7 U的出现和快速优势。这些快速的转换表明，基因组RNA的编辑发生的频率比以前认为的要高。此外，这表明EBOV/7 U表型具有与GP的受控表达和/或分泌的sGP（野生型EBOV的主要基因产物）的表达相关的选择性优势。该研究证明了在EBOV基因组RNA的编辑位点中插入和缺失尿苷的潜力，这取决于环境限制。
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.