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I recently read a bit about the mRNA-vaccines for COVID-2019. I fully understand that mRNA cannot enter the genome of a healthy person as they lack the required reverse transcriptase to transcribe RNA back into DNA. This made one question pop up in my head, though:

What about the people who do have reverse transcriptase in their body? As far as I understand it, a retrovirus like HIV does express the required proteins to form reverse transcriptase as it's part of the virus strategy to integrate itself into the human genome.

Wouldn't that mean that an HIV-positive person, upon being vaccinated using an mRNA-vaccine, could theoretically end up having the RNA-Sequence of the vaccine transcribed into their genome if reverse transcriptase is present in their cells at the right moment? Or am I missing something? Would that mean that the COVID-vaccine could essentially become the artificial equivalent of an endogenous retrovirus, even possibly immunizing future generations?

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    $\begingroup$ It’s relevant to note that all humans have reverse transcriptase from retrotransposons and mRNA can be reverse transcribed and integrated into the genome (this the mechanism by which processed pseudogenes arise). $\endgroup$
    – canadianer
    Feb 6, 2021 at 1:13
  • $\begingroup$ medicalsciences.stackexchange.com/questions/25392/… $\endgroup$
    – Fizz
    Feb 8, 2021 at 13:58
  • $\begingroup$ skeptics.stackexchange.com/a/53027/155 $\endgroup$
    – endolith
    Mar 21, 2022 at 13:20
  • $\begingroup$ "if reverse transcriptase is present" - Case is use of rev. transcr. from HIV virus by CoV. There lies some analogy in the fact that LINE1 which is a retrotransposon mentioned by canadianer above is being used by ALU elements to have themselves integrated. $\endgroup$
    – Peter Bernhard
    Mar 30, 2022 at 7:36

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Interestingly, there's recent news we may all have some reverse transcriptase activity and in some people it leads to serious disease. The specificity of that reverse transcription is not yet known, but HIV reverse transcriptase is going to require a primer binding site - basically some lysine tRNA sequence - to get started. Of course, with low odds, there may be some conceivable way to get around that by mutation, template switching, etc., but I don't know of evidence it happens.

Reverse transcription of random RNA transcripts (including the genomes of mRNA viruses that infect us) is surely a theoretical possibility, but we should bear in mind how rarely this must occur (otherwise, our genome would be even more overflowing with spam than it is).

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    $\begingroup$ The scientific PNAS article underlying the reverse transcriptase press release is available here. $\endgroup$
    – mgkrebbs
    Aug 6, 2021 at 19:34
  • $\begingroup$ Reverse transcriptase is not the whole story as I learnt. There must be "integrase" or the like to put it in (so to say). What is known about "free floating" DNA - retrotranscribed or not - "going into" host cells DNA strains? Any idea? Maybe that is rather unknown, do you know? I refer to the mechanism of integration in a narrow sense; how is viral DNA being put into (so to say) host DNA, if there is no integrase? $\endgroup$
    – Peter Bernhard
    Mar 25, 2022 at 11:38
  • $\begingroup$ @Peter Bernhard - getting the DNA into the cell is "transient transfection", while integrating it is "stable transfection". See ncbi.nlm.nih.gov/pmc/articles/PMC8067914 . I don't deny that, in the absence of a viral vector or some other trick, stable transfection of random DNA in any given cell is very rare. $\endgroup$
    – Mike Serfas
    Mar 25, 2022 at 16:59
  • $\begingroup$ "...how rarely this must occur..." If there were a working principle that integration kills the infected cells (e.g. not by apoptosis, not like cytotoxic t cells) integration might be more common, and the less searched for (as that would be a way to get back up again). $\endgroup$
    – Peter Bernhard
    Mar 30, 2022 at 7:39
  • $\begingroup$ @Mike Serfas Thank you for providing the link. You name it: "The specificity of that reverse transcription". I think it would be interesting to read more on that issue in your answer. Provided link refers to my comment above which refers to Canadianer's. That link refers to ALU as one, special specifity of LINE1, I think. Are there any others or pertaining sources you know of? $\endgroup$
    – Peter Bernhard
    Mar 30, 2022 at 8:59

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