New medical technology

China scientists report: COVID-19 RNA does not have the ability to integrate into the host genome.

  Sars-cov-2 is a highly transmissible single stranded positive strand RNA virus, which is the cause of the serious epidemic of covid-19. Sars-cov-2 is highly infectious and causes serious clinical symptoms by invading multiple organ systems. This study focuses on the possibility of integrating COVID-19 RNA genome into the genome of infected host cells.

  On August 2, 2021, Yang Yungui team of Beijing Institute of genomics, Chinese Academy of Sciences (National bioinformatics Center) and Peng Xiaozhong team of Institute of medical biology, Chinese Academy of Medical Sciences published the research results entitled comprehensive analysis of RNA SEQ and whole genome sequencing data requests no evidence for sars-cov-2 integrating into host genome online in protein & cell (this work was submitted to the preprint on June 7, 2021) [1]. This work was carried out by RNA sequencing (RNA SEQ) of human and monkey cells infected with sars-cov-2 And whole genome sequencing, it was found that there were host virus chimeric sequences in the transcriptome sequencing results of sars-cov-2 infected cells. Through in-depth study, it was determined that this kind of chimeric sequences were essentially random connecting fragments introduced in the process of library construction; Through the whole genome sequencing of host cells, it was further confirmed that there was no corresponding chimeric DNA sequence, which ruled out the possibility of integrating sars-cov-2 virus RNA genome into host DNA genome.

  Firstly, the transcriptome of sars-cov-2 infected human (293T, Huh-7 and Calu-3) and monkey cell lines (COS-7 and MA-104) were sequenced. Host virus chimeric RNA fragments (about 0.5% - 1.8% of the total reads of virus sequencing) were identified in the transcriptome sequencing results, but the repeatability of these chimeric events was very low; Further correlation analysis of the expression level of chimeric host gene showed that the frequency of chimeric events was highly correlated with its expression level. These results suggest that these chimeric events may not occur at the genomic DNA level or through transcription, but may be introduced through some random pathway.

  Further, by analyzing the whole gene sequencing results of three human cell lines, no corresponding host virus chimeric genomic DNA fragment was found in the chromosome region corresponding to the high-frequency chimeric gene, and no DNA reading segment matching the sars-cov-2 reference genome was detected from the whole genome sequencing data. The above results show that sars-cov-2 does not have the ability to integrate into the host genome, and the chimeric sequences in the transcriptome sequencing data may come from other ways, among which the random connection is the most likely in the construction of RNA sequencing library.

  In order to verify that the source of chimeric events in the transcriptome sequencing results was introduced by random connection in the library construction process, this study mixed the RNA of sars-cov-2 infected cells and uninfected zebrafish embryos, then constructed the RNA sequencing library and further sequenced the transcriptome. The results showed that in addition to the expected human virus chimeric RNA fragments, Zebrafish virus chimeric RNA fragments that could not exist under natural conditions were also detected, and the number of chimeric reading segments of different species was related to their RNA abundance ratio in the mixed samples, which proved that this kind of chimeric reading segments came from the random connection in the process of library construction.

  In conclusion, through the systematic analysis of transcriptome sequencing, whole genome sequencing and transcriptome sequencing results of mixed samples, this study ruled out the possibility of sars-cov-2 integration into the host genome (below). It is noteworthy that recently, Zhou Li Quan research group analyzed public transcriptome data and found that the expression level of retrotransposon in human cells infected with sars-cov-2 increased, The virus host chimeric RNA reading segment was identified [2]; Rudolf jaenisch research team used the research system of overexpression LINE-1 cell line to sequence the host DNA through nanopore length reading sequencing technology, and identified the event that the 3 & rsquo; terminal region of sars-cov-2 genomic RNA was integrated into the host genome through reverse transcription 【3】 Two other independent studies found that sars-cov-2 was not integrated into the host cell genome, which was consistent with the conclusion of this study. Geoffrey J. Faulkner's team also used nanopore long reading sequencing technology to sequence the DNA of sars-cov-2 infected normal HEK293T cells, and did not find any line-1-mediated sars-cov-2 genome integration signal 【4】 Majid kazemian research team also revealed the randomness and low repeatability of host virus chimeric RNA fragments by sequencing the transcriptome of sars-cov-2 infected cells [5].

  Image: transcriptome and genome sequencing reveal that New Coronavirus RNA does not have the ability to integrate into the host genome.

  Yang Yungui, researcher of Beijing Institute of genomics, Chinese Academy of Sciences (National bioinformatics Center), Yang Ying, associate researcher, and Peng Xiaozhong, researcher of Institute of medical biology, Chinese Academy of medical sciences are the co corresponding authors of this paper. Dr. Chen Yusheng, special research assistant of Beijing Institute of genomics, Chinese Academy of Sciences (National Biological Information Center), Dr. Zhang Bing, senior engineer, and researcher Lu shuaiyao, Institute of medical biology, Chinese Academy of medical sciences are the co first authors of this paper.

  It is worth mentioning that a few days ago, Cell Reports published online research related research at University of Queensland, Australia, which also did not support the integration of COVID-19 RNA into the host genome.


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