SARS-CoV-2-Host Chimeric RNA-Sequencing Reads Do Not Necessarily Arise From Virus Integration Into the Host DNA.
SARS-CoV-2-Host Chimeric RNA-Sequencing Reads Do Not Necessarily Arise From Virus Integration Into the Host DNA.
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DOI：
10.3389/fmicb.2021.676693
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发表时间：
2021
影响因子：
5.2
通讯作者：
Kassiotis G
中科院分区：
文献类型：
--
作者：
Kazachenka A;Kassiotis G
人类基因组有证据表明，逆转录病毒和其他逆转录因子以及各种RNA和DNA病毒广泛侵入。根据大量观察，最近提出RNA病毒严重急性呼吸综合征冠状病毒2（SARS-CoV-2）体细胞整合到感染细胞的DNA中的频率很高。一个关键的观察结果是SARS-CoV-2 RNA和从人类宿主DNA转录的RNA之间存在嵌合RNA测序（RNA-seq）读数。在这里，我们研究了RNA-seq文库中人-SARS-CoV-2嵌合读段的可能来源，并为其来源提供了替代解释。在SARS-CoV-2 RNA和从转染细胞系中存在的线粒体DNA或附加体腺病毒DNA转录的RNA之间也经常检测到嵌合读段，这不太可能是SARS-CoV-2整合的结果。此外，SARS-CoV-2 RNA和从核DNA转录的RNA之间的嵌合读段高度富集宿主外显子，而不是内含子或基因间序列，并且通常涉及相同的高表达宿主基因。尽管这些发现并不排除SARS-CoV-2体细胞整合，但它们仍然表明，在RNA-seq数据中发现的人-SARS-CoV-2嵌合读段可能在文库制备期间出现，并且不一定意味着SARS-CoV-2逆转录、整合到宿主DNA中并进一步转录。
The human genome bears evidence of extensive invasion by retroviruses and other retroelements, as well as by diverse RNA and DNA viruses. High frequency of somatic integration of the RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the DNA of infected cells was recently suggested, based on a number of observations. One key observation was the presence of chimeric RNA-sequencing (RNA-seq) reads between SARS-CoV-2 RNA and RNA transcribed from human host DNA. Here, we examined the possible origin specifically of human-SARS-CoV-2 chimeric reads in RNA-seq libraries and provide alternative explanations for their origin. Chimeric reads were frequently detected also between SARS-CoV-2 RNA and RNA transcribed from mitochondrial DNA or episomal adenoviral DNA present in transfected cell lines, which was unlikely the result of SARS-CoV-2 integration. Furthermore, chimeric reads between SARS-CoV-2 RNA and RNA transcribed from nuclear DNA were highly enriched for host exonic, rather than intronic or intergenic sequences and often involved the same, highly expressed host genes. Although these findings do not rule out SARS-CoV-2 somatic integration, they nevertheless suggest that human-SARS-CoV-2 chimeric reads found in RNA-seq data may arise during library preparation and do not necessarily signify SARS-CoV-2 reverse transcription, integration in to host DNA and further transcription.
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