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解析重组杆状病毒感染对哺乳动物细胞基因传递的全基因组影响。

Unraveling the Genome-Wide Impact of Recombinant Baculovirus Infection in Mammalian Cells for Gene Delivery.

机构信息

Department of Biomedical Science & Engineering, Konkuk University, Seoul 05029, Korea.

Department of Bio-Industrial Technologies, Konkuk University, Seoul 05029, Korea.

出版信息

Genes (Basel). 2020 Nov 4;11(11):1306. doi: 10.3390/genes11111306.

DOI:10.3390/genes11111306
PMID:33158084
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7694231/
Abstract

Baculovirus expression systems have been widely used to produce recombinant mammalian proteins owing to the lack of viral replication in vertebrates. Although several lines of evidence have demonstrated impacts of baculovirus infection in mammalian hosts, genome-wide effects have not been fully elucidated. Here, we provide comparative transcriptome profiles of baculovirus and host-immune response genes in recombinant baculovirus-infected mammalian and insect cells. Specifically, to decipher the impacts of baculovirus infection in mammalian cells, we conducted total RNA-seq on human 293TT cells and insect Sf9 cells infected with recombinant baculovirus. We found that baculovirus genes were rarely expressed under the control of baculoviral promoters in 293TT cells. Although some baculovirus early genes, such as and , showed limited expression in 293TT cells, baculoviral late genes were mostly silent. We also found modest induction of a small number of mammalian immune response genes associated with Toll-like receptors, cytokine signaling, and complement in baculovirus-infected 293TT cells. These comprehensive transcriptome data will contribute to improving recombinant baculovirus as tools for gene delivery, gene therapy, and vaccine development.

摘要

杆状病毒表达系统由于在脊椎动物中缺乏病毒复制而被广泛用于生产重组哺乳动物蛋白。尽管有几项证据表明杆状病毒感染对哺乳动物宿主有影响,但基因组范围的影响尚未完全阐明。在这里,我们提供了重组杆状病毒感染的哺乳动物和昆虫细胞中杆状病毒和宿主免疫反应基因的比较转录组图谱。具体来说,为了解析杆状病毒感染对哺乳动物细胞的影响,我们对感染重组杆状病毒的人 293TT 细胞和昆虫 Sf9 细胞进行了总 RNA-seq 分析。我们发现杆状病毒基因在 293TT 细胞中很少在杆状病毒启动子的控制下表达。尽管一些杆状病毒早期基因,如 和 ,在 293TT 细胞中显示出有限的表达,但杆状病毒晚期基因大多沉默。我们还发现,在感染杆状病毒的 293TT 细胞中,与 Toll 样受体、细胞因子信号和补体相关的少数几种哺乳动物免疫反应基因被适度诱导。这些全面的转录组数据将有助于改进重组杆状病毒作为基因传递、基因治疗和疫苗开发的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/e9f0e4680d18/genes-11-01306-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/21a26cf6905a/genes-11-01306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/19c36efca866/genes-11-01306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/9770d318c8fd/genes-11-01306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/6c5fbba5c092/genes-11-01306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/e9f0e4680d18/genes-11-01306-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/21a26cf6905a/genes-11-01306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/19c36efca866/genes-11-01306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/9770d318c8fd/genes-11-01306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/6c5fbba5c092/genes-11-01306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57a4/7694231/e9f0e4680d18/genes-11-01306-g005.jpg

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