钟鸣
(2022-12-31 19:23):
#paper Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues https://doi.org/10.1073/pnas.2105968118
许多新冠感染者康复后依然能通过PCR检测到病毒,但是却分离不到活病毒,考虑到新冠病毒是一种RNA病毒,因此合理怀疑其逆转录整合到了宿主基因组上。为了证实,作者使用了三种测序方法来对人类细胞来源的基因组测序,结果均发现了新冠基因组。此外作者还回顾了感染者组织来源的RNA测序数据,发现了包括新冠在内的许多病毒的转录本。比较简单的一篇论文,比较可看的地方是讨论。
IF:9.400Q1
Proceedings of the National Academy of Sciences of the United States of America,
2021-05-25.
DOI: 10.1073/pnas.2105968118
PMID: 33958444
Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues
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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.
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