Deep RNA sequencing reveal a complex transcriptional landscape of a bat adenovirus.

Bat adenoviruses are a group of recently identified adenoviruses (AdVs) which are highly prevalent in bats yet share low similarity to known AdVs from other species. In this study, deep RNA sequencing was used to analyze the transcriptome at five time points following the infection of a bat AdV in a kidney cell line derived from a myotis bat species. Evidence of AdV replication was observed with the proportion of viral RNAs ranging from 0.01% at 6 h to 1.3% at 18 h. Further analysis of viral temporal gene expression revealed three replication stages; the early stage genes encoding mainly for host interaction proteins, the intermediate stage genes for the DNA replication and assembly proteins, and the late stage genes for most structural proteins. Several bat AdV genes were expressed at stages that differed from their counterpart genes previously reported for human AdV. In addition, single-base resolution splice sites of several genes and promoter regions of all 30 viral genes were fully determined. Simultaneously, the temporal cellular gene expression profiles were identified. The most overrepresented functional categories of the differentially expressed genes were related to cellular immune response, transcription, translation, and DNA replication and repair. Taken together, the deep RNA sequencing provided a global, transcriptional profile of the novel BtAdV and the virus-host interactions, which will be useful for the understanding and investigation of AdV replication, pathogenesis and specific virus-bat interactions in future research.

蝙蝠腺病毒（Bat adenoviruses）是一类新近被鉴定的腺病毒（adenoviruses, AdVs），在蝙蝠中流行率极高，但与其他物种的已知腺病毒序列相似性极低。本研究采用深度RNA测序（deep RNA sequencing）技术，对某鼠耳蝠（myotis bat）物种来源的肾细胞系感染蝙蝠腺病毒后的五个时间点的转录组进行分析。研究观测到腺病毒复制的证据：病毒RNA的占比从感染后6小时的0.01%升至18小时的1.3%。对病毒时序基因表达的进一步分析揭示了三个复制阶段：早期基因主要编码宿主互作蛋白，中期基因编码DNA复制与组装相关蛋白，晚期基因则编码绝大多数结构蛋白。部分蝙蝠腺病毒基因的表达时相与此前报道的人腺病毒同源基因存在差异。此外，本研究完整确定了多个基因的单碱基分辨率剪接位点，以及全部30个病毒基因的启动子区域。同时，本研究还鉴定出宿主细胞的时序基因表达谱。差异表达基因中富集程度最高的功能类别主要与细胞免疫应答、转录、翻译以及DNA复制和修复相关。综上，本研究通过深度RNA测序获取了新型蝙蝠腺病毒（BtAdV）的全局转录组特征与病毒-宿主互作图谱，该成果将为未来研究腺病毒的复制机制、致病机理以及特定的病毒-蝙蝠互作模式提供重要参考。