a reply to: ancientlight
Dr. Been is excellent, he got me through immunology, molecular virology, and immunopathology in graduate school. Great supplementary material to my
courses which were ridiculous at times.
It sounds like the next step is in vivo and I don’t think you will see this unless we overexpress these proteins in the animal model with a pseudo
virus or something to generate excessive amounts of virus like knocking down STAT/JAK, ISG, or IFN, PKR etc. In vitro the cells will be heavily
targeted, there is no dilution, there is significant over expression, much more than a vaccine and even higher viral loads, and no external support
signaling which plays a significant role.
I believe what this explains better is what will happen in severe infection and this is what contributes to T cell exhaustion and faulty targeting by
B cells. Leading to less mature white blood cells and lymphocytes being recruited in a last stand.
It reminds me of oncogenic viruses and cancers or their treatments. If this happens during infection you are in trouble. Because COVID has a positive
sense genome it can spread by cell binding, endocytosis, cell to cell fusion, and by exosomes. If these cells are generating faulty targets they will
usually be destroyed or not used if they cannot be edited properly. Kind of like with the central tolerance aspect and targeting self. It could also
lead to bad targeting if one receptor is ok and the faulty one is diluted during the screening process.
Since this could contribute to ADE in natural infection and with a bad vaccine, it should’ve been looked at months ago. I don’t see it influencing
natural killer cell function very much and probably not cytotoxic T cell function which are the important controllers of most viral infections. I
could see it contributing to CD4 T cell exhaustion and these are the cells that help regulate and signal for antibody and other cell generation.
So to me it supports vaccination because you will get cytotoxic T cells that remember the spike to support natural killer cells during an infection
which should prevent this. But it also reminds us that we are cutting it way to close with this vaccine target and should work to shift it to the
replication complex or the RBD. People are having issues with it and it seems to be centered around complement, clotting, and antibody generation
which this research supports.
It’s focused on immune cells already matured and being trained on antigen targeting. Cells will be removed, cells will self destruct, or cells will
have faulty targeting in vitro. No impact on progenitor cells or effector memory cells that self renew and generate new cells. Interesting research
that raises additional questions about the 2nd and 3rd stage of COVID (pulmonary and hyper inflammation).
We could also use this as a new target to potentially prevent viral gene impacts which lead to replication and protein generation. It also shouldn’t
be an issue in most because many viruses (and potentially vaccines) could do this in a host. It’s why you don’t rush and why you don’t force.