A controversial study has demonstrated the possibility that genetic material from SARS-CoV-2 – the virus that causes COVID-19 – could integrate into our genome. The paper, published in Proceedings of the National Academy of Sciences (PNAS), perhaps provides an explanation as to why people who have recovered from COVID-19 can still test positive for the virus months later. It also builds on the findings of a much-disputed preprint by the same authors, which was released in December 2020.
The said preprint received a fair amount of skepticism from within the scientific community, with many branding it ‘dangerous’ amid fears it could spark concern that messenger RNA (mRNA)-based vaccines could alter human DNA. The authors have, however, stressed that neither set of results – preprint or PNAS – suggest this.
Subsequent preprints by other researchers have picked holes in the methodology used; one preprint illustrated that the integration of viral DNA reported in the study was likely introduced by the very technique used to detect it, and was not, in fact, a genuine integration by reverse transcription – the process of synthesizing DNA from an RNA template – as originally suggested.
Rudolf Jaenisch, PhD, and Richard Young, PhD, biology professors at the Whitehead Institute and the Massachusetts Institute of Technology, who led the work, have acknowledged and countered these criticisms. The team used three different sequencing techniques to determine whether SARS-CoV-2 RNA could be integrated into the human genome in culture, via reverse transcription, and all three approaches found evidence that it was possible. DNA copies of the viral RNA were present in the host-cells genome and were found to have been integrated by a LINE1-mediated mechanism. LINE-1 elements make up 17 percent of the human genome and are the genetic sequences that encode reverse transcriptase, the enzyme responsible for reverse transcription.
While these results seem to back up the original hypothesis, that a SARS-CoV-2 DNA fragment can be integrated into the human genome via reverse transcription, it should be mentioned that approximately 30 percent of the integrated viral DNA was missing a LINE-1 recognition site. It is possible, therefore, that another method may be responsible for the integration.
As for the clinical relevance of these findings, evidence of integration in patients is yet to be seen. However, the team do report SARS-CoV-2 integration in tissue from living and autopsied COVID-19 patients: “Importantly, such chimeric transcripts are detected in patient-derived tissues,” they write. “Our data suggest that, in some patient tissues, the majority of all viral transcripts are derived from integrated sequences. Our data provide an insight into the consequence of SARS-CoV-2 infections that may help to explain why patients can continue to produce viral RNA after recovery.”
Further research is needed as to the effect potential integration could have on the course of the disease, and also the implications this might have for other disease-causing RNA viruses, such as dengue and influenza virus.