SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2020 |
---|---|
Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
---|---|
Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 13. Dez. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Zhang, Liguo [VerfasserIn] |
---|
Links: |
---|
Themen: |
---|
Anmerkungen: |
Date Revised 09.02.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.1101/2020.12.12.422516 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM318959224 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM318959224 | ||
003 | DE-627 | ||
005 | 20231225170440.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2020 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1101/2020.12.12.422516 |2 doi | |
028 | 5 | 2 | |a pubmed24n1063.xml |
035 | |a (DE-627)NLM318959224 | ||
035 | |a (NLM)33330870 | ||
035 | |a (PII)2020.12.12.422516 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Zhang, Liguo |e verfasserin |4 aut | |
245 | 1 | 0 | |a SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome |
264 | 1 | |c 2020 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 09.02.2022 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Preprint | |
700 | 1 | |a Richards, Alexsia |e verfasserin |4 aut | |
700 | 1 | |a Khalil, Andrew |e verfasserin |4 aut | |
700 | 1 | |a Wogram, Emile |e verfasserin |4 aut | |
700 | 1 | |a Ma, Haiting |e verfasserin |4 aut | |
700 | 1 | |a Young, Richard A |e verfasserin |4 aut | |
700 | 1 | |a Jaenisch, Rudolf |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2020) vom: 13. Dez. |w (DE-627)NLM31090014X |7 nnns |
773 | 1 | 8 | |g year:2020 |g day:13 |g month:12 |
856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.12.12.422516 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |j 2020 |b 13 |c 12 |