Spike, SARS-CoV-2 and Pfizer, miR148a... an intriguing interaction!
mRNA-based vaccines have been used globally to eradicate the coronavirus-disease 2019 (COVID-19) pandemic. Vaccine efficacy and adverse reactions depend on immune responses, such as proinflammatory cytokine production and lymphocyte activation. We conducted a prospective cohort study to...
pubmed.ncbi.nlm.nih.gov
I began my reflection on the Miyashita et al. publication above... The authors correlated a decrease in miR148a with the production of anti-Spike antibodies following Pfizer anti-covid injections.
"Furthermore, miR-148a was associated with specific antibody production."
But they deduced that this down-regulation of miR148a is due to activation of dendritic cells (DCs) and antigen-presenting cells (APCs). Indeed, miR148a is known to decrease the activity of DCs and APCs... so a decrease in miR148a represents an activation of these cells, which then stimulate T-cells and B-cells.
The problem is that miR148a is involved in B-cell maturation and differentiation into long-lived plasma cells (LLPCs), and represents a key factor in the acquisition of immunotolerance in B-cells during ontogeny.
B cells undergo affinity maturation and class switch recombination of their immunoglobulin receptors during a germinal center (GC) reaction, before they differentiate into long-lived antibody-secreting plasma cells (PCs). Transcription factors such as Bach2 and Mitf are essential during this...
pubmed.ncbi.nlm.nih.gov
Autoreactive B cells play critical roles in a large diversity of autoimmune diseases, but the molecular pathways controlling these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed miRNA library and identified ...
ncbi.nlm.nih.gov
Although the cellular concentration of miRNAs is critical to their function, how miRNA expression and abundance are regulated during ontogeny is unclear. We applied miRNA-, mRNA-, and ChIP-Seq to characterize the microRNome during lymphopoiesis within ...
ncbi.nlm.nih.gov
"Previous miRNA profiling studies showed that miR-148a expression is tightly regulated throughout B cell development. miR-148a is highly expressed in pro- and pre-B cells, substantially downregulated upon differentiation into immature and mature B cells, and induced upon B cell activation and differentiation into germinal center B cells."
"miR-148a was increased upon B-cell activation and was the most abundant miRNA in mature human and murine PCs."
Thus, normally, Miyashita and colleagues would find upregulation of miR148a correlated with B cell activation and antibody production. Not a downregulation.
Moreover, miR148a impacts directly the expression of NRP-1...
MicroRNAs (miRs) are crucial regulators of vascular endothelial cell (EC) functions, including migration, proliferation, and survival. However, the role of most miRs in ECs remains unknown. Using RNA sequencing analysis, we found that miR-148a/b-3p expression ...
ncbi.nlm.nih.gov
miR-148a inhibits NRP1 expression by directly binding to the 3′UTR of NRP1 mRNA...
And the authors to conclude: "The expression of miR148a/b-3p was inversely correlated with NRP1 expression. Based on these data, we hypothesized that decreased miR-148a/b expression would upregulate NRP1 and alter endothelial cells function."
This is very interesting because NRP-1 is a receptor or co-receptor for the Spike protein...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in 2019, is responsible for the global coronavirus disease 19 (COVID-19) pandemic. The main protein that interacts with the host cell receptor is the Spike-1 (S1) subunit of the coronavirus. This subunit binds with...
pubmed.ncbi.nlm.nih.gov
The Omicron variant of SARS-CoV-2 bears peptide sequence alterations that correlate with a higher infectivity than was observed in the original SARS-CoV-2 isolated from Wuhan, China. We analyzed the CendR motif of spike protein and performed in silico molecular docking with neuropilin-1 (Nrp1)...
pubmed.ncbi.nlm.nih.gov
And the Spike protein of Omicron variants seems to have an increased affinity for NRP-1! So, if the overall level of miR148a is reduced by Pfizer's anti-covid injections, does this pave the way for greater contamination by Omicron variants? It's a possibility.
Another point is: NRP-1 is involved in the maturation of B-cells in germinal centers via Thf... therefore, Spike/NRP-1 interaction can block B-cells maturation in GCs and thus induce a memory B-cells defect.
NRP-1 plays other roles in the immune system... But this finding is ultimately congruent with the results obtained by Miyashita's team.
T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. Tfh cells regulate the differentiation and survival of activated B cells outside and inside germinal centers (GC) of secondary lymphoid organs. They act through cognate contacts with...
pubmed.ncbi.nlm.nih.gov
And now, for the virus... SARS-CoV2...
SARS-CoV-2, the novel coronavirus infection has consistently shown an association with neurological anomalies in patients, in addition to its usual respiratory distress syndrome. Multi-organ dysfunctions including neurological sequelae during COVID-19 persist even after declining viral load. We...
pubmed.ncbi.nlm.nih.gov
Using plasmids encoding the viral spike protein, Ritu Mishra et al. found exosomes containing this glycoprotein accompanied by miRNAs, including miR148a.... their target : IRF9 in the microglial cells... So, the viral Spike protein circulating in exosomes with miR148a can disturb the IFN-1 and especially IFNa... Disrupting type 1 interferons is tantamount to helping the virus, since they are normally involved in antiviral immunity. But also anti-cancer immunity!
We find ourselves in an "action/reaction" game in which anti-covid injections facilitate viral infections, and then it's the viral Spike's turn to act via miR148a.
It is known also that miR148a is implicated in cancers !
"miR-148a-3p is a tumor suppressor that is significantly downregulated in several types of cancers, including hepatocellular carcinoma, gastric cancer, and ovarian cancer. miR-148b-3p is also reported to participate in the regulation of tumorigenesis."
So wouldn't anti-covid injections promote cancer by down-regulating miR148a? It's a huge question.
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