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TRENDING OPEN SCIENCE
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SARS-CoV-2 RNA reverse-transcribed and integrated into the human
genome
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By
Liguo Zhang
Alexsia Richards
Andrew Khalil
Emile Wogram
Haiting Ma
Richard A. Young
Rudolf Jaenisch
DOI: 10.1101/2020.12.12.422516
On bioRxiv: https://biorxiv.org/content/10.1101/2020.12.12.422516v1
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-infectious. 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.
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