BRLF1-dependent viral and cellular transcriptomes and transcriptional regulation during EBV primary infection in B lymphoma cells
BRLF1-dependent viral and cellular transcriptomes and transcriptional regulation during EBV primary infection in B lymphoma cells
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B 淋巴瘤细胞 EBV 原发感染期间 BRLF1 依赖性病毒和细胞转录组以及转录调控。
DOI：
10.1016/j.ygeno.2021.05.039
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发表时间：
2021-06-09
期刊：
影响因子：
4.4
通讯作者：
Kuang, Ersheng
中科院分区：
文献类型：
--
作者：
Long, Xubing;Yang, Ziwei;Kuang, Ersheng
即早期蛋白BRLF 1在EB病毒（EBV）的裂解性感染中起重要作用，在其中它激活裂解性病毒的转录和复制。然而，BRLF 1对细胞基因表达和转录重编程的影响，在早期裂解周期的知识仍然有限。在本研究中，深度RNA测序分析确定了野生型和BRLF 1缺陷型EBV原发感染的B淋巴瘤细胞中所有差异表达基因（DEG）和可变剪接。BRLF 1依赖的细胞DEG进行了注释，主要差异富集途径与DNA复制和转录，免疫和炎症反应，受体相互作用和趋化因子信号传导和代谢过程。此外，通过质谱分析BRLF 1结合蛋白表明，BRLF 1结合并与几个转录因子和剪接体的组分合作，然后影响RNA聚合酶II依赖的转录和前mRNA剪接。病毒和细胞DEG启动子区域中的RTA结合RRE基序或独特的合作转录因子的特定基序表明BRLF 1采用不同的策略来调节病毒和细胞的转录。因此，我们的研究特征BRLF 1依赖的细胞和病毒的转录谱在原发感染，然后揭示了全面的病毒-细胞相互作用和转录的改变在EBV原发感染和裂解复制。
The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.