CONTINUED
Okay. We've now gotten enough about adaptive immunity to explain the following paper released on Oct 13, 2021.
- SARS–CoV–2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro (pdf attached, for safety get your own at the link below):
https://www.mdpi.com/1999-4915/13/10/2056
This paper looks at the intracellular distribution of the various bits that make up the SARS-CoV-2 virus. In general, a virus has a bit of DNA or RNA inside it that encodes the proteins that make up the shell (capsid) and surface (spike) proteins for the virus, but no machinery to take that code and translate it into those proteins itself. For that, it has to get the DNA or RNA (RNA in the case of Covid-19, and Coronaviruses in general) inside the cell, where it can highjack the cell's own machinery to make thousands of copies of itself, the capsid, and spike proteins, usually destroying the cell in the process. This paper looks at what happens when cells make the different types of bits for the Covid viral capsid and spike protein(s), and where those bits end up in the cell. Of all the different bits, one of these localizes predominantly in the cell nucleus – the Covid spike protein.
The paper then looks at what the spike protein does when it gets to the nucleus. The nucleus is the “library” for the cell, where all the human genomic DNA resides, and molecular “librarians” control the dispatch of copies of protein-coding genes out into the cell as messenger RNA (mRNA), to be translated into proteins that do all kinds of things. The spike protein, as it turns out, is the unwelcome library patron that interferes with the librarians in the performance of their duties. Specifically, it interferes with two “DNA repair” processes known as non-homologous end joining (NHEJ) DNA repair and homologous recombination (HR) DNA repair.
p. 4
In V(D)J recombination, the process inside immature B and T cells that creates the unique sticky ends for the outside of that cell for it to become a mature B or T cell, the V, D, and J parts of the gene for the sticky part are taken apart, modified, and put back together. This process has some randomness to it, which is where the billions of different resulting combinations arise for each unique B or T cell receptor. If “taking bits of genes apart, modifying them, and putting them back together, with randomness involved” sounds complex and scary, well, it is. If it doesn’t quite work out, the cell generally doesn’t make it. NHEJ DNA repair is necessary for the “putting them back together” part. If NHEJ is kept from happening in a maturing B or T cell, that’s a problem. If it happens in a lot of maturing B and T cells, it’s a recipe for disaster.
- Putting it all together:
Let’s follow the mRNA in the injections: It is contained in lipid nanoparticles, which are generally injected into the deltoid muscle of the upper arm. Those lipid nanoparticles do not overwhelmingly stay there, but enter the bloodstream. A nontrivial concentration of them ends up in the Bone Marrow. The mRNA in the lipid nanoparticles finds its way into developing blood cells in the bone marrow, some of which are immature B and T cells.
In all types of cells, the mRNA from the injection is translated into Covid-19 spike proteins, some of which are supposed to then get back to the bloodstream, where naïve (mature, but have never seen their antigen soulmate and started dividing to churn out progeny) B cells can say “whoa there, fella”, and make antibodies for the spike protein, which ostensibly confers some humoral (plasma antibody) immunity to the virus. Other spike proteins, however, find their way to the cell nucleus, since that’s where they seem to like to congregate.
Once in the nucleus, the spike proteins inhibit two DNA repair processes crucial to the continued integrity of every cell. For immature B and T cells in the process of undergoing V(D)J recombination, the spike protein keeps this from being successful by inhibition of one of the two processes. If this happens often enough, few new B or T cells make it to maturity, and out in the bloodstream where they can look for skullduggery. For all cells, genomic errors left unrepaired due to the failure of these repair process will eventually lead to serious issues within those cells and the cells that result from cell division.
A shortage of B and/or T cells is an immunodeficiency, one manifestation of which we know of as AIDS. Cells with cascading genomic errors leading to mis-regulated cell destruction and division fall into the category of what we know of as Cancer.
CONTINUED
Okay. We've now gotten enough about adaptive immunity to explain the following paper released on Oct 13, 2021.
- SARS–CoV–2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro (pdf attached, for safety get your own at the link below):
https://www.mdpi.com/1999-4915/13/10/2056
This paper looks at the intracellular distribution of the various bits that make up the SARS-CoV-2 virus. In general, a virus has a bit of DNA or RNA inside it that encodes the proteins that make up the shell (capsid) and surface (spike) proteins for the virus, but no machinery to take that code and translate it into those proteins itself. For that, it has to get the DNA or RNA (RNA in the case of Covid-19, and Coronaviruses in general) inside the cell, where it can highjack the cell's own machinery to make thousands of copies of itself, the capsid, and spike proteins, usually destroying the cell in the process. This paper looks at what happens when cells make the different types of bits for the Covid viral capsid and spike protein(s), and where those bits end up in the cell. Of all the different bits, one of these localizes predominantly in the cell nucleus – the Covid spike protein.
The paper then looks at what the spike protein does when it gets to the nucleus. The nucleus is the “library” for the cell, where all the human genomic DNA resides, and molecular “librarians” control the dispatch of copies of protein-coding genes out into the cell as messenger RNA (mRNA), to be translated into proteins that do all kinds of things. The spike protein, as it turns out, is the unwelcome library patron that interferes with the librarians in the performance of their duties. Specifically, it interferes with two “DNA repair” processes known as non-homologous end joining (NHEJ) DNA repair and homologous recombination (HR) DNA repair.
p. 4
In V(D)J recombination, the process inside immature B and T cells that creates the unique sticky ends for the outside of that cell for it to become a mature B or T cell, the V, D, and J parts of the gene for the sticky part are taken apart, modified, and put back together. This process has some randomness to it, which is where the billions of different resulting combinations arise for each unique B or T cell receptor. If “taking bits of genes apart, modifying them, and putting them back together, with randomness involved” sounds complex and scary, well, it is. If it doesn’t quite work out, the cell generally doesn’t make it. NHEJ DNA repair is necessary for the “putting them back together” part. If NHEJ is kept from happening in a maturing B or T cell, that’s a problem. If it happens in a lot of maturing B and T cells, it’s a recipe for disaster.
- Putting it all together:
Let’s follow the mRNA in the injections: It is contained in lipid nanoparticles, which are generally injected into the deltoid muscle of the upper arm. Those lipid nanoparticles do not overwhelmingly stay there, but enter the bloodstream. A nontrivial concentration of them ends up in the Bone Marrow. The mRNA in the lipid nanoparticles finds its way into developing blood cells in the bone marrow, some of which are immature B and T cells.
In all types of cells, the mRNA from the injection is translated into Covid-19 spike proteins, some of which are supposed to then get back to the bloodstream, where naïve (mature, but have never seen their antigen soulmate and started dividing to churn out progeny) B cells can say “whoa there, fella”, and make antibodies for the spike protein, which ostensibly confers some humoral (plasma antibody) immunity to the virus. Other spike proteins, however, find their way to the cell nucleus, since that’s where they seem to like to congregate.
Once in the nucleus, the spike proteins inhibit two DNA repair processes crucial to the continued integrity of every cell. For immature B and T cells in the process of undergoing V(D)J recombination, the spike protein keeps this from being successful by inhibition of one of the two processes. If this happens often enough, few new B or T cells make it to maturity, and out in the bloodstream where they can look for skullduggery. For all cells, genomic errors left unrepaired due to the failure of these repair process will eventually lead to serious issues within those cells and the cells that result from cell division.
A shortage of B and/or T cells is an immunodeficiency, one manifestation of which we know of as AIDS. Cells with cascading genomic errors leading to mis-regulated cell destruction and division fall into the category of what we know of as Cancer.