PT  - JOURNAL ARTICLE
AU  - Liguo Zhang
AU  - Alexsia Richards
AU  - Andrew Khalil
AU  - Emile Wogram
AU  - Haiting Ma
AU  - Richard A. Young
AU  - Rudolf Jaenisch
TI  - SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
AID  - 10.1101/2020.12.12.422516
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.12.422516
4099  - http://biorxiv.org/content/early/2020/12/13/2020.12.12.422516.short
4100  - http://biorxiv.org/content/early/2020/12/13/2020.12.12.422516.full
AB  - Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious1–14. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.Competing Interest StatementThe authors have declared no competing interest.