State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Sci Adv. 2021 Jun 23;7(26). doi: 10.1126/sciadv.abf8962. Print 2021 Jun.
Like most DNA viruses, herpesviruses precisely deliver their genomes into the sophisticatedly organized nuclei of the infected host cells to initiate subsequent transcription and replication. However, it remains elusive how the viral genome specifically interacts with the host genome and hijacks host transcription machinery. Using pseudorabies virus (PRV) as model virus, we performed chromosome conformation capture assays to demonstrate a genome-wide specific trans-species chromatin interaction between the virus and host. Our data show that the PRV genome is delivered by the host DNA binding protein RUNX1 into the open chromatin and active transcription zone. This facilitates virus hijacking host RNAPII to efficiently transcribe viral genes, which is significantly inhibited by either a RUNX1 inhibitor or RNA interference. Together, these findings provide insights into the chromatin interaction between viral and host genomes and identify new areas of research to advance the understanding of herpesvirus genome transcription.
与大多数 DNA 病毒一样，疱疹病毒精确地将其基因组递送到受感染宿主细胞的精细组织的核中，以启动随后的转录和复制。然而，病毒基因组如何特异性地与宿主基因组相互作用并劫持宿主转录机制仍然难以捉摸。我们使用伪狂犬病病毒 (PRV) 作为模型病毒，通过染色体构象捕获实验证明了病毒与宿主之间的全基因组特异性跨物种染色质相互作用。我们的数据表明，PRV 基因组由宿主 DNA 结合蛋白 RUNX1 递送至开放染色质和活跃转录区。这有利于病毒劫持宿主 RNAPII 以有效地转录病毒基因，而 RUNX1 抑制剂或 RNA 干扰显著抑制这一过程。总之，这些发现深入了解了病毒和宿主基因组之间的染色质相互作用，并确定了新的研究领域，以促进对疱疹病毒基因组转录的理解。
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