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Comprehensive analysis of RNA-seq and whole genome sequencing data reveals no evidence for SARS-CoV-2 integrating into host genome

Yu-Sheng Chen, Shuaiyao Lu, Bing Zhang, Tingfu Du, Wen-Jie Li, Meng Lei, Yanan Zhou, Yong Zhang, Penghui Liu, Yong-Qiao Sun, Yong-Liang Zhao, Ying Yang, Xiaozhong Peng, Yun-Gui Yang
doi: https://doi.org/10.1101/2021.06.06.447293
Yu-Sheng Chen
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
3Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
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Shuaiyao Lu
4National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan China
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Bing Zhang
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
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Tingfu Du
4National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan China
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Wen-Jie Li
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
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Meng Lei
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
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Yanan Zhou
4National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan China
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Yong Zhang
4National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan China
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Penghui Liu
4National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan China
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Yong-Qiao Sun
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
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Yong-Liang Zhao
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
5University of Chinese Academy of Sciences, Beijing 100049, China
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Ying Yang
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
3Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
5University of Chinese Academy of Sciences, Beijing 100049, China
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  • For correspondence: ygyang@big.ac.cn pengxiaozhong@pumc.edu.cn yingyang@big.ac.cn
Xiaozhong Peng
4National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan China
6State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing China
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  • For correspondence: ygyang@big.ac.cn pengxiaozhong@pumc.edu.cn yingyang@big.ac.cn
Yun-Gui Yang
1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2China National Center for Bioinformation, Beijing 100101, China
3Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
5University of Chinese Academy of Sciences, Beijing 100049, China
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  • For correspondence: ygyang@big.ac.cn pengxiaozhong@pumc.edu.cn yingyang@big.ac.cn
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Abstract

SARS-CoV-2, as the causation of severe epidemic of COVID-19, is one kind of positive single-stranded RNA virus with high transmissibility. However, whether or not SARS-CoV-2 can integrate into host genome needs thorough investigation. Here, we performed both RNA sequencing (RNA-seq) and whole genome sequencing on SARS-CoV-2 infected human and monkey cells, and investigated the presence of host-virus chimeric events. Through RNA-seq, we did detect the chimeric host-virus reads in the infected cells. But further analysis using mixed libraries of infected cells and uninfected zebrafish embryos demonstrated that these reads are falsely generated during library construction. In support, whole genome sequencing also didn’t identify the existence of chimeric reads in their corresponding regions. Therefore, the evidence for SARS-CoV-2’s integration into host genome is lacking.

One-Sentence Summary SARS-CoV-2 does not integrate into host genome through whole genome sequencing.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 07, 2021.
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Comprehensive analysis of RNA-seq and whole genome sequencing data reveals no evidence for SARS-CoV-2 integrating into host genome
Yu-Sheng Chen, Shuaiyao Lu, Bing Zhang, Tingfu Du, Wen-Jie Li, Meng Lei, Yanan Zhou, Yong Zhang, Penghui Liu, Yong-Qiao Sun, Yong-Liang Zhao, Ying Yang, Xiaozhong Peng, Yun-Gui Yang
bioRxiv 2021.06.06.447293; doi: https://doi.org/10.1101/2021.06.06.447293
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Comprehensive analysis of RNA-seq and whole genome sequencing data reveals no evidence for SARS-CoV-2 integrating into host genome
Yu-Sheng Chen, Shuaiyao Lu, Bing Zhang, Tingfu Du, Wen-Jie Li, Meng Lei, Yanan Zhou, Yong Zhang, Penghui Liu, Yong-Qiao Sun, Yong-Liang Zhao, Ying Yang, Xiaozhong Peng, Yun-Gui Yang
bioRxiv 2021.06.06.447293; doi: https://doi.org/10.1101/2021.06.06.447293

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