Evidence map›Paper›PMID 33958444›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues.

Liguo Zhang, Alexsia Richards, M Inmaculada Barrasa, Stephen H Hughes, Richard A Young, Rudolf Jaenisch

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 1 pooled it
17.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

144 citing papers in PubMed, 1 synthesis or guideline pooled it, 296 citations in OpenAlex.

  1. JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022
    Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. COVID-19 and Lung Cancer Interactions: A Literature Review.Medical sciences (Basel, Switzerland) · 2025
    Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Advancing Precision Medicine: Recent Innovations in Gene Editing Technologies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  20. Article

84 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Liguo ZhangWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Alexsia RichardsWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
M Inmaculada BarrasaWhitehead Institute for Biomedical Research, Cambridge, MA 02142.ORCID 0000-0003-3393-4814
Stephen H HughesHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.ORCID 0000-0002-9176-4377
Richard A YoungWhitehead Institute for Biomedical Research, Cambridge, MA 02142.ORCID 0000-0001-8855-8647
Rudolf JaenischWhitehead Institute for Biomedical Research, Cambridge, MA 02142; jaenisch@wi.mit.edu.
Whitehead Institute for Biomedical Research · USNational Cancer Institute · US

Funding

IntegraseZIABC011426 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HUGHES, STEPHEN H · 2012 to 2022
$14.0M
Virology Core: MIT Center for Human Tissue Models for Infectious Diseases (MIT.HTMID)U19AI131135 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GEHRKE, LEE · 2017 to 2021
$8.7M
Transcriptional condensates, epigenetic editing and Rett SyndromeR01MH104610 · NIMH · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF, YOUNG, RICHARD · 2014 to 2023
$7.4M
Intramural NIH HHSNIAID NIH HHS U19 AI131135NIH HHS 1U19AI131135-01NIH HHS 5R01MH104610-21NIMH NIH HHS R01 MH104610
6 · The paper itself

Abstract

Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and recurrence of PCR-positive tests have been widely reported in patients after recovery from COVID-19, but some of these patients do not appear to shed infectious virus. We investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the DNA of human cells in culture and that transcription of the integrated sequences might account for some of the positive PCR tests seen in patients. In support of this hypothesis, we found that DNA copies of SARS-CoV-2 sequences can be integrated into the genome of infected human cells. We found target site duplications flanking the viral sequences and consensus LINE1 endonuclease recognition sequences at the integration sites, consistent with a LINE1 retrotransposon-mediated, target-primed reverse transcription and retroposition mechanism. We also found, in some patient-derived tissues, evidence suggesting that a large fraction of the viral sequences is transcribed from integrated DNA copies of viral sequences, generating viral-host chimeric transcripts. The integration and transcription of viral sequences may thus contribute to the detection of viral RNA by PCR in patients after infection and clinical recovery. Because we have detected only subgenomic sequences derived mainly from the 3' end of the viral genome integrated into the DNA of the host cell, infectious virus cannot be produced from the integrated subgenomic SARS-CoV-2 sequences.

Indexed as

AnimalsChlorocebus aethiopsCOVID-19Genome, ViralHEK293 CellsHumansRNA, ViralSARS-CoV-2Vero CellsVirus IntegrationVirus ReplicationRNA, Viralchimeric RNAsgenomic integrationLINE1reverse transcriptionSARS-CoV-2

Identifiers

PMID33958444
PMCPMC8166107
OpenAlexW3158782420

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.