Hi
@Daffodil,
@M Paine re: that article that said EBV could be eliminated after years of antivirals, I can't see that happening...no one has ever been able to replicate that and no other paper mentions it.
Yes, I would tend to agree with you there. It's like with HIV, there are very, very few cases where complete eradication has been observed. In latent state, infected cells are basically not visible to the immune system. In order to clear all infected cells, every single infected cell must switch from latency to lytic infection. I have not seen any information about how possible something like that is.
The ONLY mention of EBV eradication I have come across is after stem cell transplantation and the person just picked it up again from their spouse.
I wonder if you might have meant bone marrow transplant? That sounds interesting, but yes EBV is so ubiquitous in the general population. I doubt many people could expect to clear the virus, and remain clear of it without some sort of continued intervention, continued antivirals, or moving to Antarctica
So since people who get full blown mono are more likely to have autoimmune disease, does that mean those people just get a bigger dose of the virus and have more B cells with the latent virus in it?
When you say get a bigger dose, I think you mean end up with a higher amount of latent infected b-cells, that's an interesting idea. I'm sure that in time we might know more about the relationship between the rate of latent infection, and the incidence of auto-immunity. If I had to guess, I'd say there's a relationship between the two. There are other factors at play, such as genetic susceptibility to EBV, and which B-cell's happen to get infected, happen to become activated and go on to proliferate and differentiate. I don't think just because a person becomes heavily infected, that they would go on to develop abhorrent b-cell responses.
I guess the thing is, we still don't really understand how tolerance is broken (how auto-immunity occurs and gets around the bodies systems in place to avoid that from happening). It's not clear the mechanism by which a person can generate auto-immunity, and why those genes are factors. We just know those genes are likely to be involved by looking at the genetics of patients who have certain auto-immune diseases.
Then again, there are several people I know of who remain in remission with antiretrovirals too.
The thing is, a lot of people go into remission without any treatment. Without some sort of blinded trial, there's no way to know if the antiretrovirals are doing anything. Recently, the Rituximab trials are a really good example of this. Anecdotal evidence was extremely prominent that the treatment was helpful, but blinded trials were not successful. I feel like we should really be careful even with Valtrex to give too much faith in any recovery being related to any specific treatment, but that said... I'm still taking it.
In more direct answer to your following question about antiretrovirals:
Could these drugs affect the EBV NA2 activity or the binding of NA2?
Presumably a drug would need to function
inside the nucleus of the cell to interact with EBV NA2. DNA sits inside the nucleus, and the nuclear pore is a small regulated entry/exit point which limits what can come in/go out. DNA genes are transcribed from DNA into RNA which leaves the nucleus, to then be translated into proteins. I don't know how likely it is that an anti-retroviral drug would function inside the nucleus. That's were the interaction of EBV NA2 would be happening. EBV enters the cell nucleus during lytic infection.
Retroviruses are special, because they integrate with the host's own DNA. They need to bring with them a reverse-transcriptase (RT) when infecting a new cell, and that is a common drug target. I think that generally occurs outside the nucleus in the cytoplasm of the cell. For that reason, I don't know that anti-retrovirals would interact with EBV NA2.
If there are only a small percentage of B cells with the virus in it, how can this affect gene expression to such an extent as to cause a severe disease? sorry probably a silly question....
I don't think that's a silly question. B-cells are pretty complicated if you ask me. You probably know most or at least part of this, but as a re-cap. B-cells go through phases of their life... starting out from bone-marrow as a naive cell which doesn't produce antibody. The antibody it does have is on the surface of the cell. Eventually the antibody on the surface might happen to bind strongly against something another immune cell shows it. If that occurs, it triggers a sequence of events which leads to many, many more cloned b-cells being produced which no longer have that original antibody on the cell surface, but an even 'better' version of the antibody which is much better at binding to that antigen (see affinity maturation). Each of those matured b-cell clones just constantly spits out antibodies all day long.
Those clones likely won't all be infected with EBV anymore, but what if something goes wrong during affinity maturation and peripheral tolerance is broken?
In that way, you can go from a single b-cell, to an enormous amount of antibodies being produced. In answer to your question, that is why a relatively small population of broken b-cells can translate into a severe disease. That is because it only takes one b-cell to undergo affinity maturation, break tolerance, and become activated to cause disease. I think that's rather simplistic, and probably trivialises what is a really uncommon event.
An analogy might be cancerous cells. In most cases, cancer originates from a single cell which has become 'cancerous' enough to proliferate and multiply uncontrollably, evading the immune system, securing a blood supply, ignoring the signals to kill itself. It just takes one, but because cells divide and amplify themselves, it becomes a disease.
Cheers,
Mark
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