SARS-CoV2 Spike Protein Expression in Mice Causes Damage via Innate Immune System (Update 158)

coronavirus Spike

protein

activated natural

immune

response

damage

d heart muscle cells welcome to another

update

from Medcram Covid-19, that's the title of an article about new research that was presented at the American Heart Association but has not yet been published published, which we are going to talk about This research basically shows first of all that the

spike

protein

in heart muscle cells is directly toxic and that it does not need the ace2 receptor to cause the

damage

in question, as you know, there has been a lot of talk on the cardiovascular complications of SARS

cov2

. and covid-19, even in some of the vaccines there have been some reports and studies showing inflammation of the heart tissue known as myocarditis, so as always we will go ahead and put the links in the description below to all of these articles and studies Let's talk, but let's get to what these researchers actually did.

This study was conducted at the Masonic Medical Research Institute in Utica, New York, and the study's lead author and assistant professor was Dr. Ju Chung Lin. What they did was they looked at a mouse model and they wanted to infect

mice

in two different ways to show the difference between the Spike protein and other Coronavirus Spike proteins, specifically SARS

cov2

and another human coronavirus. Now the first thing you need to understand is that mouse cells have an ace2 receptor, but it is completely different from the H2 receptor that we see in humans, in fact, the ace2 receptor in

mice

does not interact in any way with the H2 protein.

spike

in SARS cov2, the next thing they did was I took a viral vector now let me explain a little bit what a viral vector is.

A viral vector is basically a way of delivering genetic information to the cell to which you want to deliver it and that viral vector is capable of infecting that cell and transmitting that genetic material to the nucleus of the cell in this case they used the Adeno Associated virus type 9 which It's a to v nine and if you want to know more about a dental associated virus vector I point you to this research article that just came out in March of this year that actually shows that it may actually be a way of introducing the covid-19 virus into cells to develop antibodies, so if you want to understand more about how these virus vectors are used, this might give you more information in terms of what we're going to talk about, I think this would be a great article and we'll put it in the link next, so what we are doing here is setting two different conditions, as you can see, we have a virus.

Vector here on the left and a viral vector here on the right and we're going to infect the same type of cells. The first thing they did was clone the Spike protein from the SARS cov2 virus which is now in the transcript presented at the American Heart Association. they didn't specify which variant they cloned, in other words, it could have been Omicron, it could have been Delta, it could have been Alpha Beta P1, it could have been the original, we don't know what spike protein they were referring to, hopefully it came out in the manuscript and Once they obtained the Spike protein sequence, they put it into the viral vector as a portion of the DNA and did the same with a human coronavirus.

This is a virus that would give you a cold. has some breathing problems, but it would never cause any problems with his heart hcovnl63, so they sequenced that Spike protein and included that DNA in the viral vector, so of course these viral vectors have Spike proteins on their surface and a dot The key thing to understand here is that the Spike proteins from both respective viruses actually interact with the ace2 receptor in humans, but they do not interact with the ace2 receptor in mice, so this is important to understand. Let me tell you that again both Spike proteins can interact with the ace2 receptor in humans, but neither of these interact with the ace2 receptor on the surface of heart cells in mice, so what happens is that the viral vectors infect the heart cells. mice and the DNA enters the nucleus where it becomes double-stranded and then begins to be transcribed into messenger RNA, the messenger RNA then produces the spike proteins and the spike proteins, of course, are placed on the surface of the cells and, Of course, to be clear, I'm drawing a line here because these are two different events that are happening, but I'm showing it as one here and I'm just breaking it down to show you that this is happening here on the left in a situation and this it's happening here on the right in a different situation and so those cells that are infected with aav9 with the SARS cov2 Spike, of course, produce spike proteins on the surface, they also have some, of course, in the cytoplasm. and some of them are actually secreted into the extracellular space and that happens not only with SARS cov2 Spike but also with humans. kovi nl63 as well and of course I want to reinforce here that the ace2 enzyme in this particular mouse cell is not being deactivated.

Nothing is happening to the ace2 receiver. Here the ace2 receptor continues to function normally because, again, none of these Spike proteins that you see. anywhere on this page are interacting with the mouse ace2 receptor. What happens next, what they found is that there were a number of proteins and inflammation that occurred here with the SARS cov2 Spike protein, but not with the hcov nl63 spike experiment on the right side. They discovered that there were a number of proteins along with the spike protein here on the left, specifically called toll-like receptor 4. So what is the toll-like receptor?

It's a protein that's attached to natural killer cells and that tells natural killer cells. that this is something that should not be there, it is part of the

innate

immune

system

, it does not require prior infection, this is something that

innate

ly the immune

system

knows that it should not be there and goes after it in addition to all these four toll type receptors. there was a lot of inflammation and also enlargement of these cells, so the cells grew in size, became dysfunctional and also became inflamed and if you want to read more about toll-like receptors on natural killer cells in their application for immunotherapy and some basic information About This you can read here in this article, which will be linked in the description below, but just to satisfy some of your curiosity, here you can see that it was initially speculated that the cells involved in the innate immune system response They were not specific and eliminated microbes without However, there is presensitization.

Studies have reported that innate immune cells recognize microbial associated or pathogenic molecular patterns and that is exactly what is happening here on this side, but it is not happening in this experiment where there is a regular spike protein hcov nl63 which means let's say there is something in The spike protein after it is created in the natural environment of the heart cell in mice

causes

a reaction that has nothing to do with turning off the ace2 receptor. Let me say that again there is something specifically about the spike protein. with SARS cov2 that is not the same as the spike protein which by the way hits the same receptor in humans the ace2 receptor something different that does not cause inflammation here but it does here so there must be a protein or a pathogen associated molecular pattern or pamp which is triggering the response here on this side but is not triggering the response here on this side and again because the ace2 receptor in mice is different from that in humans and because none of these Spike proteins affect the ace2 receptor and mice We cannot say that it is a mediated inflammatory reaction.

What the authors of this study do not know is if it is the Spike protein that is attached to the cell surface or if it is soluble proteins that cause this reaction to occur. and that will be the source of more information shortly. The question is whether this is the mechanism that is happening right now with myocarditis and inflammatory heart conditions in patients who get SARS cov2 and it could also be some of the reasons why people who get vaccinated also get heart inflammation . It is worth noting at this point that not all people with SARS cov2 get inflammation of the heart muscle and certainly not all people who receive the SARS Kobe 2 vaccine get inflammation of the heart muscle, so the question is what What

causes

some people to get it and some not, of course there are differences in genetics, there are differences in environment, there may be differences in the amount of Spike protein, there are also some questions about the type of Spike protein, here we said that The Spike protein of SARS cov2 was sequenced. and it's the reason we have this Spike protein in this viral vector.

We don't know which SARS Kobe 2 variant it was. What about the spike protein derived from the vaccine? Well, it turns out that the Spike protein is sequenced and put into vaccines. specifically the modern one, the Pfizer one, the Johnson and Johnson one, and the Novovax one, are actually significantly different in a specific way from the spike protein in SARS cov2. Now, that would be enough to make a difference or not, we don't know, that study hasn't been done. done for those of you who are regular Med Cram listeners will know that the Spike protein was specifically designed in vaccines to remain in the prefusion complex, work done by Jason MccLellan of the University of Texas at Austin and his work was specifically used in the development of both mRNA vaccines, the Johnson Johnson vaccine and also the Novovax vaccine, and specifically the purpose of that was to keep the spike protein fused to a specific confirmation so that it would be more immunogenic in that confirmation, the spike protein. that we see in SARS cov2 is not fused into that position, but is very wobbly and can take many different types of positions and if you are interested in learning more about that particular topic and listening to a presentation by Jason MccLellan and how he came to find out this and what the techniques were, we'll put a link to the video where he describes exactly what he's doing.

The other interesting thing about this is the fact that if you're going to have inflammation in the heart, it's the heart. the muscle cells themselves that need to produce the spike protein and for that to happen, you actually have to have viral particles that reach the heart and that implies, of course, a viremia that involves obtaining viral particles in high enough concentrations so that They really spill into the blood. and of course this is something that happens in people who contract SARS cov2 in a very severe way, where the virus replicates in multiple places in the body and grows exponentially.

Of course, there has been a question about whether or not this is the same as This happens in those who receive the vaccine, so vaccines that enter the muscle cells in the arm, for example, enter the blood supply and there has been a debate and a question about whether syringe aspiration is useful or not in this situation. to prevent vaccine nanoparticles specific to mRNA vaccines from entering the blood supply, but what's interesting is that the particular types of patients who get myocarditis from mRNA vaccines are specifically those young gentlemen who get it after their second dose and that would want us to believe that if people were to get the shot into the blood, it shouldn't be specifically in younger people, but it should be distributed evenly, so that goes against that theory, the other aspect of This is It is interesting to note that in this study it is the innate immune system that is causing the inflammation, as we have said, the innate immune system does not require prior exposure, it understands that these pathogen-associated protein molecules are something that they know is innate. .

It seems to me that you would see the reaction equally after the first or second injection, whereas on the second injection you get a more adaptive immune response where you have antibodies that are now forming that would be more likely to cause the inflammation, so It is not clear whether or not this study answers all of these questions. I think it raises some very interesting points, but there is still definitive work to be done to say whether or not this is the mechanism for why we are seeing myocarditis in some people who receive vaccines early on, especially in younger people and in men and Of course, as we've said before, there have been no studies done on the spike protein that is derived from vaccines in this type of setting and I think that type of study should be done because, as we've already mentioned, the spike protein vaccine is deliberately different from the SARS cov2 spike and this study was specifically looking at the SARS cov2 spike and that's interesting again because When we look at the cells of the immune system, we notice that the innate immune system is the immune system that weakens with age, so the innate immune system will be very powerful when you're young and, as we've talked about before, it produces things like, for example,natural killer cells, monocytes, all of these things are involved in the production of interferon, which is the body's way of protecting itself against viral infections in the early stages of infection.

It's interesting to me because, generally, these are people who have had very serious situations. Infections are the most likely to suffer from the heart complications of the virus, so it almost seems like the innate immune system is being slowed down and not allowed to work early on, but then as the immune system becomes suppressed , the virus spreads and Only then is the innate immune system allowed to do what it needs to do and this is not new to those who have seen Medcram and will know. We have talked about this before. You can see it here in a letter written by Nancy.

She writes here. The SARS and myrrh studies suggest that the interferon response is delayed compared to coronaviruses that cause mild illness and to milder cases of these two coronaviruses. that can cause severe illness, patients with severe SARS or MERS had higher viral loads and delayed responses to interferon, so let's pause there compared to our coronavirus nl63 which only affects the lungs, this is one of those mild cases which do not seem to delay the interferon response, this is what is said here in an article that was published at the beginning of the pandemic, however, there is something about SARS cov2 that delays the innate immune response, could that be the reason Why are we seeing a difference between SARS?

Spike protein cov2 and Spike protein ml-63 is that there is something in the SARS spike protein cov2 that is delaying the innate immune response. Moving on, it could be that the patients most susceptible to severe disease are those who cannot mount an effective early antiviral. immune response A study of 50 patients with cases ranging from mild to severe found that gene

expression

profiles indicating type 1 and type 2 interferon responses were highest in patients with mild to moderate disease and were low in patients with severe disease o critical a similar difference in patients' serum type 1 interferon activity was detected, patients with more severe disease had less type 1 interferon activity in the blood.

Now remember that type 1 interferon activity is a result of the innate immune system, so let's back up again, think about this. Could it be that the reason we are seeing more damage to the SARS Spike Kobe 2 protein is that the innate immune system has been turned off early and is now arriving late while the virus has had a chance to reach the heart? that is possible, well let's look here at the innate immune system and type 1 interferon activity, as you can see here very clearly, those who had very good responses of the innate immune system had mild disease compared to those who had low responses of the innate immune system who had a critical illness.

It is possible that this innate immune system is being suppressed and slowed down from the beginning and that is causing severe illness and only after that point do you start to see an increase in the innate immune system and inflammation of the heart muscle. We've seen that In a number of studies, here's another study that was published in science that shows that people who had mutations in their innate immune system had their ability to produce interferon, which they found caused inflammation with toll-like receptors in natural killer cells. Well, let's get all that out of the way.

OK, what happened? There is no innate immune system response and these are the people without exception who had severe Covet 19. Those who had antibodies against interferon response again had no response to interferon. These also had very severe Covid. -19 comes out, so the bottom line is that there is a lot of data, there is a lot of research that hasn't been published yet, so we don't have the details on exactly what type, for example, variant they used in the SARS cov2 Spike protein in the Viral vector, we don't know if it is the soluble Spike protein that is causing this or if it is the Spike protein that is specifically attached to the cell membrane and again, we don't know why the vast majority of people who get SARS cov2 never get it inflammation of the heart and In fact, the vast majority of people who get vaccinated do not suffer from inflammation of the heart muscle.

This probably doesn't explain everything, but it raises more questions, and that's exactly what we want in science: questions so we can do more research. and get more answers I want to thank you for joining us please subscribe turn on notifications and join us at medcram.com for continuing medical education on topics such as ECG interpretation, basic chemistry metabolic panel 7 results, and CBC results they explain clearly thank you for joining us