Exogenous Coronavirus Interacts With Endogenous Retrotransposon in Human Cells.
Exogenous Coronavirus Interacts With Endogenous Retrotransposon in Human Cells.
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外源性冠状病毒与人类细胞中的内源性反转录转座子相互作用。
DOI：
10.3389/fcimb.2021.609160
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发表时间：
2021
影响因子：
5.7
通讯作者：
Zhou LQ
中科院分区：
文献类型：
--
作者：
Yin Y;Liu XZ;He X;Zhou LQ
由影响鸟类和哺乳动物呼吸道的冠状病毒引起的疾病在全球范围内的爆发有所增加。最近危险的冠状病毒是MERS-CoV，SARS-CoV和SARS-CoV-2，导致呼吸道疾病，甚至几个器官衰竭。然而，冠状病毒对宿主细胞的深刻影响仍然难以捉摸。在这项研究中，我们分析了MERS-CoV，SARS-CoV和SARS-CoV-2感染的人肺源性细胞的转录组，并观察到这些冠状病毒的感染都诱导逆转录转座子表达增加，泰特基因上调。在SARS-CoV-2感染的人肠道类器官中也观察到逆转录转座子的上调。反转录转座子上调可导致基因组不稳定性增加和具有来自反转录转座子的通读的基因的表达增强。因此，逆转录转座子基础水平较高的人，如癌症患者和老年人，可能会增加有症状感染的风险。此外，我们的证据支持逆转录转座子上调的长期表观遗传。我们还观察到反转录转座子与SARS-CoV-2 RNA的嵌合转录产物为潜在的人类基因组入侵病毒片段，其中SARS-CoV-2基因组的前部和后部更容易形成嵌合RNA。因此，我们建议在病毒基因组中间设计核酸检测的引物和探针，以更高的概率识别活病毒。总之，我们提出了我们的假设，即冠状病毒侵入人体细胞并与逆转录转座子相互作用，在患有基础疾病的患者中引发更严重的症状。在冠状病毒感染患者的治疗中，可能有必要更多地关注逆转录转座子失调造成的潜在危害。
There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.