Controversial basic research: “Each type of RNA in a cell has the ability to enter the genome”

Controversial basic research: "Each type of RNA in a cell has the ability to enter the genome"

In some people who have recovered from COVID-19, the genetic remnants of Sars-CoV-2 can be detected even weeks after the infection has subsided. This idea may be because that coronaviruses move into human DNA, quite unconventional. How did you come up with the investigation?
I was sitting with my old friend and colleague Rick Young with a glass of wine on a small island in Maine and we let our thoughts fly. We had heard of recovered COVID patients who were discovered to have traces of Sars-CoV-2 genetic material weeks after illness, and we wondered why this might be. Because we had both previously dealt with retroviruses, which are routinely incorporated into the genomes of their hosts, we eventually came up with the idea: What if Sars-CoV-2 manages to do this too?

But Sars-CoV-2 is not a retrovirus, it lacks the tools to rewrite the virus genome, RNA into DNA and then insert it into human DNA. How is coronavirus supposed to do this without this special tool?
In the human genome with elements that survived previous retrovirus infections—such as the retrotransposon LINE1, a fragment of the genome that can reproduce itself. It contains a template for a protein called reverse transcriptase that can transcribe RNA into DNA. The enzyme does this with LINE1 blueprints and human RNA snippets that are nearby – or with fragments of virus RNA if the whole thing is in infected cells. They are added to the LINE1 sequence, resulting in their inclusion in the human genome.

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You know for sure?
And. we tracked the whole way. Originally we only detected mixed RNA in infected people, some viruses, some humans. This has yet to reassure many colleagues. It turned out that viral RNA and human RNA can coexist even when isolated from cells. In that case, our discovery would be nothing more than a laboratory artifact that does not occur naturally. This is why over the past few months we have spent a great deal of time investigating the different stages of the establishment process in cells. Among other things, we also looked directly at the DNA of cells that we had previously infected with the virus and at the same time supplied with LINE1 elements. There we found not only virus sequences, but also segments immediately adjacent to them that could only be formed if the retrotransposon was included.

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But if you equip cells with excess amounts of LINE1 and then incorporate snippets of the virus genome into the DNA, that doesn’t mean it also happens under natural conditions without this biochemical nudge.
This is true, so we also examined infected cells without artificially amplifying LINE1 elements. They had fewer fragments of the virus genome, but they also had them.

What components of the virus genome are made of?
Often we find components of the N-protein – this is the protein inside viruses that helps package their RNA. It is arguable that it would appear most often, likely, as most copies of this RNA are present while the virus is being assembled.

Could this really explain why virus genes are found in some healthy people for so long? PCR tests never detect the entire virus, but only small snippets a dozen blocks long. If only fragments of the virus are included, then it must be a great coincidence that this fragment of all things has the short sequence that is found in PCR tests?
It’s certainly rare that the two come together. But it simply means that there must be many more cases of people having fragments of the virus in the genetic material of some of their cells after infection. In some cases, they are not detected because the section the PCR detects was not included at all. And partly because it may not be the mucous membrane cells in the throat that are used in the smear that are left over from the integrated virus sequences.

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Which cells might otherwise contain fragments of the virus?
The virus can affect not only the lungs but also many different cell types, such as the intestines, liver, and heart. We do not yet know whether the integration of viruses into these cells can also take place.

But even if they do, do most infected cells die?
Infected lung cells almost all die, so changes in genetic material are rarely permanent here. It may be different in other tissues. We are investigating it now.

Rudolf Janisch used to do research in Hamburg. Today he leads a laboratory group at the Whitehead Institute in Cambridge, Massachusetts…Photo: Whitehead Institute

Antibodies were found in long covid patients that react to both the patient’s own cells and the coronavirus. Could this be a reaction to a mixed protein that resulted from the incorporation of viral and human protein blueprints into the genome?
I focused on work. Assuming that human genes supplemented with virus building blocks will produce proteins for the cell surface, some of which contain the body’s own blueprints, some of which are viral, then one would expect an heritable response from the immune system. Can do. A protein that combines viral properties with the body’s own tissue characteristics may also stimulate an immune response that is directed against one’s own body. Maybe – this is pure speculation.

There are some indications that Long-Covid is an autoimmune reaction. And could this be because the genomes of many recovered people are haunted by remnants of the virus?
As I said, this is pure speculation, we still cannot estimate how often cells survive with this kind of virus. But it is understandable.

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If viral RNA can enter the genome, can the RNA from Biotech and Moderna’s COVID-19 vaccines also get lost in the genome?
I think it is very unlikely, but it cannot be ruled out.

But you haven’t checked it, you’re guessing here?
Yes. Every type of RNA in a cell has the ability to enter the genome, and this is probably a completely normal biological process as well. But the important thing to emphasize is that A vaccination contains much less RNA than an infection – millions or even billions of times less. Accordingly the vaccine is very unlikely to contain RNA. And if it does, I still wouldn’t worry. Vaccination may work better if the vaccine protein lasts longer. In any case, compared to everything that happens in the body with Sars-CoV-2 infection, this is a negligible risk. In any case, I just had a second vaccination last week – without any theoretical abdominal pain.

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