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No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing

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 (>50x) 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.

Type Journal
ISBN 2211-1247 (Electronic)
Authors 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.
Responsible Garvan Author Dr Ira Deveson
Publisher Name Cell Reports
Published Date 2021-08-31
Published Volume 36
Published Issue 7
Published Pages 109530
Status Published in-print
DOI 10.1016/j.celrep.2021.109530
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/34380018