Departments of Chemical and Structural Biology and Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Bioinformatics Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Sci Rep. 2024 Oct 29;14(1):25894. doi: 10.1038/s41598-024-76078-6.
Mimivirus bradfordmassiliense (Mimivirus) is a giant virus that infects Acanthamoeba species - opportunistic human pathogens. Long- and short-read sequencing were used to generate a de novo transcriptome of the host and followed the dynamics of both host and virus transcriptomes over the course of infection. The assembled transcriptome of the host included 22,604 transcripts and 13,043 genes, with N50 = 2,372 nucleotides. Functional enrichment analysis revealed major changes in the host transcriptome, namely, enrichment in downregulated genes associated with cytoskeleton homeostasis and DNA replication, repair, and nucleotide synthesis. These modulations, together with those implicated by other enriched processes, indicate cell cycle arrest, which was demonstrated experimentally. We also observed upregulation of host genes associated with transcription, secretory pathways and, as reported here for the first time, peroxisomes and the ubiquitin-proteasome system. In Mimivirus, the early stages of infection were marked by upregulated genes related to DNA replication, transcription, translation, and nucleotide metabolism, and in later stages, enrichment in genes associated with lipid metabolism, carbohydrates, and proteases. Some of the changes observed in the amoebal transcriptome likely point to Mimivirus infection causing dismantling of host cytoskeleton and translocation of endoplasmic reticulum membranes to viral factory areas.
米米病毒布拉德福德马西利恩斯(Mimivirus)是一种感染变形虫属(Acanthamoeba)物种的巨型病毒,变形虫属是人类机会性病原体。本研究采用长读长和短读长测序方法,对宿主进行从头转录组测序,并对感染过程中宿主和病毒转录组的动态变化进行了跟踪。组装的宿主转录组包含 22604 条转录本和 13043 个基因,N50=2372 个核苷酸。功能富集分析揭示了宿主转录组的重大变化,即与细胞骨架稳态和 DNA 复制、修复和核苷酸合成相关的下调基因富集。这些调节,以及其他富集过程所暗示的调节,表明细胞周期停滞,这在实验中得到了证实。我们还观察到与转录、分泌途径相关的宿主基因上调,以及这里首次报道的与过氧化物酶体和泛素-蛋白酶体系统相关的宿主基因上调。在米米病毒感染的早期阶段,与 DNA 复制、转录、翻译和核苷酸代谢相关的上调基因显著,而在后期阶段,与脂质代谢、碳水化合物和蛋白酶相关的基因富集。阿米巴转录组中观察到的一些变化可能表明米米病毒感染导致宿主细胞骨架解体和内质网膜向病毒工厂区域的易位。