Genomic RNAs of Borna disease virus are elongated on internal template motifs after realignment of the 3′ termini
Genomic RNAs of Borna disease virus are elongated on internal template motifs after realignment of the 3′ termini
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DOI：
10.1073/pnas.1016759108
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发表时间：
2011-04-26
影响因子：
11.1
通讯作者：
Schneider, Urs
中科院分区：
文献类型：
--
作者：
Martin, Arnold;Hoefs, Nadja;Schneider, Urs
博尔纳病病毒 (BDV) 基因组 (vRNA) 和反基因组 (cRNA) 的末端结构与其他负链 RNA 病毒不同，因为这两种分子在 3' 末端均具有四个核苷酸，而在相反链的 5' 末端没有明显的模板。因此，v-和cRNA分子并不是完美的镜像，这种情况与维持遗传信息的传统策略不兼容。我们在此表明，从缺乏非模板核苷酸的 cDNA 中回收的重组病毒可以有效地重建 3' 突出端。对潜在替代模板序列中编码遗传标记的重组病毒的分析表明，BDV v-和 cRNA 分子通过分别位于紧邻 v-和 cRNA 3' 端的内部模板基序上的重新排列和延伸过程来延伸。数据进一步表明，cRNA 延伸仅限于新生链的单个模板基序，而 vRNA 的延伸可能使用多个模板基序。我们提出，3'末端的延长支持了BDV持久性期间基因组RNA分子的末端完整性，并且还提供了一种优雅的策略来消除BDV v-和cRNA 5'末端的三磷酸基团，而不损害病毒的遗传信息。
The terminal structures of the Borna disease virus (BDV) genome (vRNA) and antigenome (cRNA) differ from those of other negative strand RNA viruses, as both molecules possess four nucleotides at the 3' terminus without an apparent template at the 5' end of the opposite strand. Consequently, the v-and cRNA molecules are not perfect mirror images, a situation that is not compatible with conventional strategies to maintain genetic information. We show here that recombinant viruses recovered from cDNA lacking the nontemplated nucleotides efficiently reconstitute the 3' overhangs. Analyses of recombinant viruses encoding genetic markers in potential alternative template sequences demonstrated that the BDV v-and cRNA molecules are extended by a realign-and-elongation process on internal template motifs located in close proximity to the 3' ends of v-and cRNA, respectively. The data further suggest that cRNA elongation is restricted to a single template motif of the nascent strand, whereas elongation of vRNA might use multiple template motifs. We propose that the elongation of the 3' termini supports the terminal integrity of the genomic RNA molecules during BDV persistence, and furthermore provides an elegant strategy to eliminate the triphosphate groups from the 5' termini of the BDV v-and cRNA without compromising the genetic information of the virus.