Do coronavirus genes slip into human chromosomes?

This is a topic that I hope someone with a scientific background in molecular cell biology
can shed light on. The title comes from an article in the May 14th issue of Science Magazine.
As the article states, these results in no way imply that those (mRNA COVID) vaccines
integrate their sequences into our DNA and even if this happens rarely that doesn't
necessarily imply any clinical effects.

How would a SARS CoV-2 infection be able to penetrate the nuclear membrane?

The authors of the article explain how reverse transcriptase could be available in cells
with many copies of LINE-1 elements.

"SARS-CoV-2, the virus that causes COVID-19, has genes composed of RNA, and Jaenisch, Young, and co-authors contend that on rare occasions an enzyme in human cells may copy the viral sequences into DNA, allowing them to slip into our chromosomes. The enzyme, reverse transcriptase, is encoded by LINE-1 elements, sequences that litter 17% of the human genome and represent artifacts of ancient infections by retroviruses. In their original preprint, the researchers presented test tube evidence that when human cells spiked with extra LINE-1 elements were infected with the coronavirus, DNA versions of SARS-CoV-2's sequences nestled into the cells' chromosomes."


https://science.sciencemag.org/content/372/6543/674

A team of prominent scientists has doubled down on its controversial hypothesis that genetic bits of the pandemic coronavirus can integrate into our chromosomes and stick around long after the infection is over. If they are right—skeptics have argued that their results are likely lab artifacts—the insertions could explain the rare finding that people can recover from COVID-19 but then test positive for SARS-CoV-2 again months later. The team, however, doesn't yet have direct evidence of the integrations in infected people or any data indicating such events harm a person's health.

Stem cell biologist Rudolf Jaenisch and gene regulation specialist Richard Young of the Massachusetts Institute of Technology, who led the work, triggered a Twitter storm in December 2020, when their team first presented evidence for this phenomenon in a preprint on bioRxiv. The researchers emphasized that viral integration did not mean people who recovered from COVID-19 remain infectious. But critics charged them with stoking unfounded fears that COVID-19 vaccines based on messenger RNA (mRNA) might somehow alter human DNA. (Jaenisch and Young stress that their results, both original and new, in no way imply that those vaccines integrate their sequences into our DNA.)

 

It’s an interesting idea. We believe around 8-10% of current human DNA is of viral origin—specifically retrovirus genetic material. It’s this DNA of viral origin that potentially codes for the reverse transcriptase these researchers think may allow viral SARS-CoV-2 RNA to be converted to DNA and subsequently incorporated into the genome.

The DNA of viral origin that currently exists in the human genome we believe in some cases is responsible for disease such as multiple sclerosis. On the other hand, viral origin DNA codes for proteins that facilitate placental formation without which there would be no mammalian reproduction.

While we are just starting to understand the roles of viral DNA in humans, there is a bit of evidence I think points to this incorporation of SARS-CoV-2 genes into human cells as unlikely. When we study the genome of individual humans, we don’t find viral genes in one person that don’t exist in others. We have found groups of people who have inherited unique viral genes compared to other groups. But if it were common for individuals to have coronavirus (non retrovirus) “genes” inserted we would see variations at the individual level, not just at the population level. Of course this is assuming the insertion of viral genes is happening in reproductive cells. If the insertions are not happening in reproductive cells and being passed on to progeny we should see genetic variation between individual cells of each person. We don’t see that either, so I think even if theoretically possible, what these researchers are proposing is rare indeed.

This is my opinion based on what we do know about viral origin genes in humans, which really isn’t much. We have a lot to learn.

 

Here's the study: https://www.pnas.org/content/118/21/e2105968118

Some things to note:

1. The cells were infected with the virus, not just exposed to LINE-1 elements.
2. They didn't indicate which parts of the viral genome were integrated.

The important part about number 1 is that it's not enough to just have reverse-transcribed DNA around. For it to be integrated into the host cell genome, there have to also be endonucleases present to cut the host DNA and allow the viral genetic material to be inserted. From what I can recall from my genetics and molecular biology classes, those are normally only present in human cells during cell division (for fixing replication errors). Being infected can mess up a cell's normal behavior, though, and some viruses code for endonucleases for this exact purposes (though I don't think SARS-CoV-2 does).

Anyway, the second point is important because even with the necessary enzymes to reverse-transcribe RNA and then cut the host genome, endonucleases don't normally just cut both stands at the same point. Instead, they cut at palindromic points. As such, only a sequence of DNA with a similar sequence at its ends is likely to be integrated at such a point. So with a full retroviral genome available for possible matches, the odds are higher compared to the small bit of RNA that is in the vaccines.

Finally, even if this was a risk, it would only happen in a tiny handful of cells in a vaccinated individual, and those cells would be destroyed by your immune system. The whole point of the vaccine is your cells produce part of the spike protein, present it on their membrane, and your immune system treats them like infected cells. They get destroyed, and you make antibodies for the real thing. So it's not like a cell or two having their DNA changed would do anything, because they won't last long enough to replicate and that change wouldn't just randomly populate to the rest of the cells in your body.

Anyway, that's all based off of what I learned while getting a molecular biology degree that I never ended up using. So my info may be 15 or so years out of date.

 

I got interested in this subject when someone started a thread by an article from Dr. Doug Corrigan's blog about how the mRNA COVID vaccines could permanently alter genomic DNA. I challenged the
OP but I didn't know much about the technical details. I read a number of articles debunking this and I found this at the Science-based Medicine site which has quite a bit to say.

The preprint that is mentioned has now passed the peer-review process and is in the May 25th issue of PNAS that can be found in the previous post. The Abstract looks like they are presenting impressive evidence but some of it is from cell cultures. "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". Maybe the immune systems of those patients where patient-derived-tissues were examined could not destroy all of the infected cells. Some scientists have published an article in Science
Magazine claiming that the viral-host chimeric transcripts are artifactual and
background noise. Other scientists claim that the incidence of host-chimeric
transcripts exceeds background noise.


https://sciencebasedmedicine.org/covid-19-vaccines-versus-purity-of-essence/

Make no mistake, the central claim of this preprint, namely that the RNA from SARS-CoV-2, the coronavirus that causes COVID-19, is somehow reverse transcribed into DNA and then finds its way into the nucleus to integrate with genomic DNA, is a truly extraordinary claim given that coronaviruses are not retroviruses like HIV and that endogenous human reverse transcription is very rare and limited, as described in depth here. Basically, only certain genetic elements in the genome can use reverse transcription to copy themselves elsewhere. It’s not as though a random coronavirus can hijack this mechanism for itself and plop its sequences somewhere in the human genome. To demonstrate that would require extraordinary evidence, particularly given that coronaviruses kill the cells they infect as they replicate.

Let’s just say that this preprint (still a preprint four months after having been published) doesn’t even come close to extraordinary evidence. Heck, it’s not even good ordinary evidence. Again, if you want the details, I refer you to this fine explanation by Ed Nirenberg. For one thing, the assumption that “persistently positive PCR” for COVID-19 must mean reverse transcription of the virus and integration is a leap. There are other mechanisms, such as the maintenance of a viral reservoir within an immunologically privileged site or immunological suppression. These are all mechanisms that have been observed in other viruses. As for the results themselves, Nirenberg makes a compelling case that the findings could well be due to an artifact of the methods used to look for viral sequences. I’ll also point out again now Nirenberg’s correct observations, as I did then, that, even if the authors had observed actual reverse transcription and integration into the genome, it would mean exactly nothing for RNA vaccines because:

• The sequence would behave like a processed pseudogene, lacking any ability to recruit host transcription machinery and would sit in the genome, quiescent.
• If the sequence somehow inserted downstream of a promoter sequence that could recruit transcription machinery, the cell would express spike protein, be recognized by the immune system, and then be killed.
• If the sequence inserted itself into the middle of gene (specifically in the middle of an exon), you would get a mutant protein that had sequences from SARS-CoV-2 that would be processed by antigen-presenting machinery and trigger a T cell response that killed the cell.

None of this stops antivaxxers from latching onto this study as “proof” that mRNA vaccines really can “permanently alter” your DNA and then to go on to engage in all sorts of predictions based on speculation:

 

I agree with all of the above. I was thinking today (you correctly point out SARS-CoV-2 doesn’t have the ability to “lyse and splice” genes) about a possible co-infection with HIV. The HIV virus has all kinds of tricks it can play at the cellular level. It’s the overachiever of retroviruses. Such a co-infection would potentially have the entire toolbox to accomplish insertion of SARS genes into the DNA.

 

I see you’ve thought of the HIV angle as well. Interesting subject. Thanks for starting the thread.

 

Yeah, that would be bad. IIRC, though, it's extremely uncommon for a cell to be infected by multiple viruses. Most viruses include mechanisms to effectively disable the membrane proteins of their host cells that are used by most viruses to infiltrate the cell.

 

I agree it’s uncommon. We saw that with influenza and Covid. I believe the prevailing theory right now is competition for resources as the overarching mechanism but I haven’t read up on recent research. I know co-infections with influenza and SARS-CoV-2 are documented but I never saw any data on what was found at the individual cell level. As you say, I doubt individual cells had simultaneous active replication of both viruses.

 

Incidentally, viral DNA in modern genomes is one way we know about evolutionary relationships. Humans share these genes with other animals, more so with the more closely related ones and vice versa.

It is also a very rare thing for it to wind up a permanent feature like this, since it evidently requires that a sperm (or egg?) be infected by such a virus, so that the material can then be incorporated into the genetic sequence of the entire organism rather than just occurring in a few cells in one individual.