Global bidirectional transcription of the Epstein-Barr virus genome during reactivation.
Global bidirectional transcription of the Epstein-Barr virus genome during reactivation.
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重新激活期间 Epstein-Barr 病毒基因组的全局双向转录。
DOI：
10.1128/jvi.02989-13
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发表时间：
2014
影响因子：
5.4
通讯作者：
Flemington,ErikK
中科院分区：
文献类型：
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作者：
O'Grady,Tina;Cao,Subing;Strong,MichaelJ;Concha,Monica;Wang,Xia;SplinterBondurant,Sandra;Adams,Marie;Baddoo,Melody;Srivastav,SudeshK;Lin,Zhen;Fewell,Claire;Yin,Qinyan;Flemington,ErikK
EB病毒（EBV）的再活化涉及参与感染性病毒体产生的约90个病毒基因的有序诱导。使用链特异性RNA-seq来评估再激活过程中的EBV转录组，我们发现了几乎在整个基因组中延伸的广泛的双向转录。相反，目前只有4%的EBV基因组是双向注释的。大多数新发现的转录区域几乎没有显示编码潜力的证据，支持大多数这些RNA的非编码作用。基于先前的细胞长非编码RNA大小计算，我们估计在再活化过程中表达的EBV基因可能比先前已知的多数百个。有限的5 ′和3 ′ cDNA末端快速扩增（RACE）实验和通过RNA-seq发现的新剪接事件表明，病毒基因组在再活化过程中的复杂性可能更大。对某些EBV潜伏基因位点的反义转录物的进一步分析表明，它们是"晚期"基因，它们是核基因，并且它们倾向于定位于其他人发现新合成的病毒基因组的核区域。这增加了这些转录本执行诸如新基因组加工、稳定、组织等功能的可能性，在再活化过程中发现明显更复杂的EBV转录组改变了我们对病毒生产过程的看法，从几乎完全由先前鉴定的病毒蛋白促进和调节的过程改变为还涉及大量病毒编码的非编码蛋白的贡献的过程。重要信息EB病毒（EBV）是一种疱疹病毒，感染世界上大多数人口，在极少数情况下会引起严重的疾病，如淋巴瘤和胃癌。使用链特异性RNA-seq，我们研究了EBV再活化过程中的病毒基因表达，并发现了比以前已知的多数百个病毒转录本。选择性剪接的发现和重叠转录物的普遍存在表明了额外的复杂性。大多数新发现的转录区域不编码蛋白质，而是可能作为非编码RNA分子发挥作用，这些分子可能参与调节基因表达、基因剪接甚至病毒基因组加工等活动。这些发现拓宽了我们理解病毒制造过程所需考虑的范围。随着更详细的研究的进行，它们可能会改变我们对整个过程的看法。
Epstein-Barr virus (EBV) reactivation involves the ordered induction of approximately 90 viral genes that participate in the generation of infectious virions. Using strand-specific RNA-seq to assess the EBV transcriptome during reactivation, we found extensive bidirectional transcription extending across nearly the entire genome. In contrast, only 4% of the EBV genome is currently bidirectionally annotated. Most of the newly identified transcribed regions show little evidence of coding potential, supporting noncoding roles for most of these RNAs. Based on previous cellular long noncoding RNA size calculations, we estimate that there are likely hundreds more EBV genes expressed during reactivation than was previously known. Limited 5′ and 3′ rapid amplification of cDNA ends (RACE) experiments and findings of novel splicing events by RNA-seq suggest that the complexity of the viral genome during reactivation may be even greater. Further analysis of antisense transcripts at some of the EBV latency gene loci showed that they are “late” genes, they are nuclear, and they tend to localize in areas of the nucleus where others find newly synthesized viral genomes. This raises the possibility that these transcripts perform functions such as new genome processing, stabilization, organization, etc. The finding of a significantly more complex EBV transcriptome during reactivation changes our view of the viral production process from one that is facilitated and regulated almost entirely by previously identified viral proteins to a process that also involves the contribution of a wide array of virus encoded noncoding RNAs.IMPORTANCEEpstein-Barr virus (EBV) is a herpesvirus that infects the majority of the world's population, in rare cases causing serious disease such as lymphoma and gastric carcinoma. Using strand-specific RNA-seq, we have studied viral gene expression during EBV reactivation and have discovered hundreds more viral transcripts than were previously known. The finding of alternative splicing and the prevalence of overlapping transcripts indicate additional complexity. Most newly identified transcribed regions do not encode proteins but instead likely function as noncoding RNA molecules which could participate in regulating gene expression, gene splicing or even activities such as viral genome processing. These findings broaden the scope of what we need to consider to understand the viral manufacturing process. As more detailed studies are undertaken they will likely change the way we view this process as a whole.