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No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing.
Cell Rep. 2021 08 17; 36(7):109530.CR

Abstract

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.

Authors+Show Affiliations

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia.Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia; Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia.School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.GENYO, Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research, PTS Granada 18016, Spain; MRC Human Genetics Unit, Institute of Genetics and Cancer (IGC), University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia.School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France.Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia; Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, QLD 4072, Australia.School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia; Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, QLD 4072, Australia.Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia; Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: faulknergj@gmail.com.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34380018

Citation

Smits, Nathan, et al. "No Evidence of Human Genome Integration of SARS-CoV-2 Found By Long-read DNA Sequencing." Cell Reports, vol. 36, no. 7, 2021, p. 109530.
Smits N, Rasmussen J, Bodea GO, et al. No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing. Cell Rep. 2021;36(7):109530.
Smits, N., Rasmussen, J., Bodea, G. O., Amarilla, A. A., Gerdes, P., Sanchez-Luque, F. J., Ajjikuttira, P., Modhiran, N., Liang, B., Faivre, J., Deveson, I. W., Khromykh, A. A., Watterson, D., Ewing, A. D., & Faulkner, G. J. (2021). No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing. Cell Reports, 36(7), 109530. https://doi.org/10.1016/j.celrep.2021.109530
Smits N, et al. No Evidence of Human Genome Integration of SARS-CoV-2 Found By Long-read DNA Sequencing. Cell Rep. 2021 08 17;36(7):109530. PubMed PMID: 34380018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing. AU - Smits,Nathan, AU - Rasmussen,Jay, AU - Bodea,Gabriela O, AU - Amarilla,Alberto A, AU - Gerdes,Patricia, AU - Sanchez-Luque,Francisco J, AU - Ajjikuttira,Prabha, AU - Modhiran,Naphak, AU - Liang,Benjamin, AU - Faivre,Jamila, AU - Deveson,Ira W, AU - Khromykh,Alexander A, AU - Watterson,Daniel, AU - Ewing,Adam D, AU - Faulkner,Geoffrey J, Y1 - 2021/07/28/ PY - 2021/06/04/received PY - 2021/07/21/revised PY - 2021/07/22/accepted PY - 2021/8/12/pubmed PY - 2021/8/26/medline PY - 2021/8/11/entrez KW - COVID-19 KW - L1 KW - LINE-1 KW - SARS-CoV-2 KW - hepatitis B virus KW - retrotransposon SP - 109530 EP - 109530 JF - Cell reports JO - Cell Rep VL - 36 IS - 7 N2 - A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/34380018/No_evidence_of_human_genome_integration_of_SARS_CoV_2_found_by_long_read_DNA_sequencing_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(21)00961-X DB - PRIME DP - Unbound Medicine ER -