Exogenous Coronavirus Interacts With Endogenous Retrotransposon in Human Cells

Frontiers in Cellular and Infection Microbiology

Xiao-zhao Liu¹  Ximiao He¹  Ying Yin²  Li-quan Zhou³ 

[1] Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Center for Genomics and Proteomics Research, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, China;Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Center for Genomics and Proteomics Research, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, China;Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;

关键词: coronavirus;    retrotransposon;    SARS-CoV-2;    TET;    long interspersed nuclear element;   

DOI  :  10.3389/fcimb.2021.609160

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY