"Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome"

[Shanti1]

I've been taking Valacyclovir 1g 3x/day for 5 months now with great benefit. My ME/CFS isn't gone, but my function level improved and lymph node swelling and sore throat have disappeared.
I would love to see a vaccine become available. In looking at www.clinicaltrials.gov, it seems like many have tried, and presumably failed since they didn't post results. But many vaccine attempts are not prophylactic, but trying to target the EBV induced cancer. Here is a recruiting phase 1 study for an EBV vaccine being given to both EBV+ and EBV- individuals: https://clinicaltrials.gov/ct2/show/NCT04645147?term=vaccine&cond=ebv&draw=2&rank=1

 

[godlovesatrier]

What brand do you take @Shanti1 ?

Not sure if you saw my other thread. Moderna have just entered an ebv vaccine into phase 1 trials and the cmv vaccine is already in phase 3. So we should see cmv sooner than ebv.

But I thought it was quite exciting.

 

[Shanti1]

What brand do you take @Shanti1 ?

Not sure if you saw my other thread. Moderna have just entered an ebv vaccine into phase 1 trials and the cmv vaccine is already in phase 3. So we should see cmv sooner than ebv.

But I thought it was quite exciting.

Yes, I saw the post on Moderna's EBV vaccine, even though it looks like it is designed to prevent infection, I would still want to try it in the hopes that it would kick my system into recognizing the EBV. I'm one of the rare people who felt better from the COVID vaccine and booster, presumably because it helped rev up my Th1 immunity. If I remember, you didn't do so well with it.

For the valacyclovir, I take a dark blue generic "F83". When I was in the first month of my prescription, it was once filled with a white generic instead of the blue and I noticed that I reacted significantly more to the white version, so they notated my prescription to always fill it with the blue.

When I first started it, wasn't sure I would be able to take it and I was only able to take 1 each day. Even with that, I had a low-grade fever most of the time and fatigue, but the fact that my lymph node swelling went down the first week, and a change in the nature of my fatigue made me persist. It took 3 months to get up to 3g a day and I would still feel poorly for about two hours after taking it.

Eventually, the fevers subsided and now I take 3g per day as if it were nothing. I'm always hesitant to automatically attribute a reaction to a herx, but I think that is what happened. I think when the antiviral disrupted the viral replication, my immune system began to recognize the virus leading to symptoms. Presumably, my viral load is now much reduced.

 

[godlovesatrier]

Thanks for the photo.

I've got generic which is light blue not dark like yours. But I do have another manufacturer I've never opened. I just had a look, these are the two I have, based on your description they both sound like generic ones.

I'm interested mainly because I do not tolerate the blue 93 one above, makes me really unwell with horrible side effects.

I had the total opposite reaction to you, valtrex just made me high, depressed and very energy unstable (oxymatrine did the same thing so it makes sense to me that possibly all drugs will effect me equally possibly regardless of infection too, hard to say). But as you say I had a very bad reaction to both az vaccines so it would appear my physiology doesn't tolerate them, as it is with drugs. However as per Cort's HR poll and analysis, it's pretty common to have those reactions amongst ME patients.

I forgot to say the moment I take valtrex generic (blue one) I get extremely dizzy and this didn't improve much with continued intake (last time I took it for 7 weeks with persistent symptoms but just felt worse and worse and worse and more and more energy unstable). It's such a huge contrast to most people. At the same time dizziness was always my primary ME symptom, fatigue and PEM were there too but the dizziness was always the worst symptom I would say. That dizziness tends to come and go but it comes back on exertion 100% of the time and it doesn't feel like POTS or OI (from my own interpretation of those diseases),

Someone on s4me posted a response to a neutropenia thread suggesting that low neutrophils suggest a viral infection, this isn't the first time I've heard this. It does make me wonder what I might be like if I could get my hands on non generic valtrex, but I haven't a clue where to get it from.

 

[GlassCannonLife]

Yes, I saw the post on Moderna's EBV vaccine, even though it looks like it is designed to prevent infection, I would still want to try it in the hopes that it would kick my system into recognizing the EBV. I'm one of the rare people who felt better from the COVID vaccine and booster, presumably because it helped rev up my Th1 immunity. If I remember, you didn't do so well with it.

For the valacyclovir, I take a dark blue generic "F83". When I was in the first month of my prescription, it was once filled with a white generic instead of the blue and I noticed that I reacted significantly more to the white version, so they notated my prescription to always fill it with the blue.

When I first started it, wasn't sure I would be able to take it and I was only able to take 1 each day. Even with that, I had a low-grade fever most of the time and fatigue, but the fact that my lymph node swelling went down the first week, and a change in the nature of my fatigue made me persist. It took 3 months to get up to 3g a day and I would still feel poorly for about two hours after taking it.

Eventually, the fevers subsided and now I take 3g per day as if it were nothing. I'm always hesitant to automatically attribute a reaction to a herx, but I think that is what happened. I think when the antiviral disrupted the viral replication, my immune system began to recognize the virus leading to symptoms. Presumably, my viral load is now much reduced.
View attachment 45748

That's great @Shanti1 ! What level roughly on the energy scale (eg bell or whichever you prefer) were you at before vs now?

 

[Manuel]

I believe there is a paper from 1997-1999 (can't recall exactly sorry!) that looked at long term, around 12 monthly, valaciclovir use in healthy people with prior EBV exposure (plus a placebo control). They saw that the proportion of latently infected B cells decreased over time, with an approximate half life of 8 months.

Wouldn't that suggest that long term use of antivirals can essentially "catch" the cells as they transition from latent to lytic periodically, slowly reducing the population of latently infected cells?

In healthy people, such treatment could be feasible since they control the cells with EBV type I latency, which are the ones that are mainly causing the problem. Therefore, they can reduce this population indirectly with the long-term use of antivirals. The antivirals prevent viral reactivation and in the meantime EBV-specific CD4 T cells are eliminating the latency I cells. In contrast, patients with alleles susceptible to infection cannot detect and eliminate these latency I cells well, as CD4 T-cell activation is impaired by gp42 disrupting the MHC-II-TCR interaction.
Therefore, even if these patients take antivirals, CD4 T cells would still not eliminate this population of latency I cells.
Another thing is that antivirals help to avoid viral reactivations and to prevent the number of infected cells from increasing. In other words, they would help to reduce outbreaks and some symptoms but they would not cure.

 

[Shanti1]

@godlovesatrier
These are the white valacyclovir I didn't do so well with:

After an initial period of fever, I also did well with oxymaitrine and currently take 3 per day with each dose of valacyclovier. The overseas pharmacies I am aware of only sell the generic, so brand would probably need a prescription. From other posts, I gather that is hard where you are.
If it is useful, here is a post I made on EBV management strategies:
https://forums.phoenixrising.me/thr...strategies-dr-nik-hedberg.85869/#post-2372939
To be honest, the only thing that seemed to help me was the medication. I react to most things on the list, and the studies are mostly in vitro, so who knows if they can reach a therapeutic concentration in a cell, but still something to consider.

That's great @Shanti1 ! What level roughly on the energy scale (eg bell or whichever you prefer) were you at before vs now?

Prior to valacyclovier I was between a 40-50 on Bell and now I am a 70. Valacyclover played a big part, but I don't think I would have gotten to a 70 with out the additional help from oxymaitrine and supplemental oxygen and my good response to the COVID vaccine. I don't do any type of exertional activity as I'm afraid it will relapse me.

 

[GlassCannonLife]

That's very interesting, thanks @Manuel

@Shanti1 that's awesome, so pretty much from moderate to mild? I have 2 months worth of valaciclovir ready to try just waiting until I stabilise at the moment.. I'm currently at around a 20 so any improvement would be amazing.

 

[Shanti1]

@GlassCannonLife yes, I went from moderate to mild on Bell. I'm fortunate in that the only virus that has shown up for me is EBV. I may have a past mycotoxin issue as well that set me up for EBV, I'm also working through that. I hope you get a response to the valacyclovir.

 

[GlassCannonLife]

In healthy people, such treatment could be feasible since they control the cells with EBV type I latency, which are the ones that are mainly causing the problem. Therefore, they can reduce this population indirectly with the long-term use of antivirals. The antivirals prevent viral reactivation and in the meantime EBV-specific CD4 T cells are eliminating the latency I cells. In contrast, patients with alleles susceptible to infection cannot detect and eliminate these latency I cells well, as CD4 T-cell activation is impaired by gp42 disrupting the MHC-II-TCR interaction.
Therefore, even if these patients take antivirals, CD4 T cells would still not eliminate this population of latency I cells.
Another thing is that antivirals help to avoid viral reactivations and to prevent the number of infected cells from increasing. In other words, they would help to reduce outbreaks and some symptoms but they would not cure.

Just thinking about this more - so in
pwME that don't have those risk alleles, we would expect the "healthy" type of clearing of latently infected cells?

 

[Treeman]

Another thing is that antivirals help to avoid viral reactivations and to prevent the number of infected cells from increasing. In other words, they would help to reduce outbreaks and some symptoms but they would not cure.

Hi, if anti virals are been taking over time (maybe several years) would people with CD4 T-cell impairment still recover when the infected cells naturally die off and new cells replaced are virus free?

 

[MartinK]

can antivirals effects may boost IFN-lambda or other IFNs @Manuel ?
Have you researched it too? Dr Chia probably knows something about that ... so i wonder if you came across it during research.

 

[Learner1]

In healthy people, such treatment could be feasible since they control the cells with EBV type I latency, which are the ones that are mainly causing the problem. Therefore, they can reduce this population indirectly with the long-term use of antivirals. The antivirals prevent viral reactivation and in the meantime EBV-specific CD4 T cells are eliminating the latency I cells. In contrast, patients with alleles susceptible to infection cannot detect and eliminate these latency I cells well, as CD4 T-cell activation is impaired by gp42 disrupting the MHC-II-TCR interaction.
Therefore, even if these patients take antivirals, CD4 T cells would still not eliminate this population of latency I cells.
Another thing is that antivirals help to avoid viral reactivations and to prevent the number of infected cells from increasing. In other words, they would help to reduce outbreaks and some symptoms but they would not cure

How can one determine which group one is in?

I was on valgancyclovir from 2017-2019 for EBV, HHV6 and CMV. Then, I had dental surgery and COVID vaccines, and HHV6 reactivated, but EBV and CMV stayed negative in multiple tests. Valganciclovir AND famciclovir beat back the HHV6.

I am wondering if the long term use if antivirals was able to reduce the EBV as you say. How do I know? And why, if EBV and CMV stayed quiet, did HHV6 reactivate?

 

[Manuel]

Just thinking about this more - so in
pwME that don't have those risk alleles, we would expect the "healthy" type of clearing of latently infected cells?

Here we try to identify the EBV subgroup. Those with other alleles could be from another subgroup due to another pathogen and the genetic factors could be different. However, if another pathogen is causing the development of ME/CFS in other subgroups, they could also be immunosuppressed causing problems with EBV latency not being able to control it.

 

[Manuel]

Hi, if anti virals are been taking over time (maybe several years) would people with CD4 T-cell impairment still recover when the infected cells naturally die off and new cells replaced are virus free?

No matter how much antivirals are taken, they do not eliminate latency I cells, nor will CD4 T cells be able to eliminate them. Since they do not go to the cause of the problem which is the alteration in the interaction between MHC-II/Gp42 and the TCR of these lymphocytes. In other words, there will always be a reservoir of this type of latency.
The only thing that antivirals could do is to inhibit reactivations and give the immune system time to control the other types of EBV latency. There if they would be useful. The rest of the latency types if we are able to recognize them, that is why there is no serious chronic EBV infection. However, if the recognition of other types of latency begins to fail or immunosuppression increases, that is when cancer appears. The increase of cells with EBV latency or the infection of cells from other tissues that present antigens of that tissue, can cause the appearance of autoimmune diseases by interfering gp42 in the antigenic presentation in patients with HLA-II alleles susceptible to EBV.

 

[Manuel]

can antivirals effects may boost IFN-lambda or other IFNs @Manuel ?
Have you researched it too? Dr Chia probably knows something about that ... so i wonder if you came across it during research.

Care must be taken with interferons. EBV is a very clever virus and takes advantage of the increase in IFN-γ produced during the antiviral response to infect new cells. Since IFN-γ enhances the immune response by increasing the expression of MHC-II in cells so that they present more antigens. This increase in MHC-II is exploited by EBV to infect new cells through gp42-MHCII interaction that previously did not express it.

 

[Manuel]

How can one determine which group one is in?

I was on valgancyclovir from 2017-2019 for EBV, HHV6 and CMV. Then, I had dental surgery and COVID vaccines, and HHV6 reactivated, but EBV and CMV stayed negative in multiple tests. Valganciclovir AND famciclovir beat back the HHV6.

I am wondering if the long term use if antivirals was able to reduce the EBV as you say. How do I know? And why, if EBV and CMV stayed quiet, did HHV6 reactivate?

Regardless of the pathogen by which ME/CFS develops, it may be that by having some immunosuppression in all subgroups, they all end up having problems with EBV. That is why taking long-term antivirals against herpesviruses may help many to reduce symptoms. Pursuing complete cure is another matter. If one belongs to the EBV subgroup and manages to eliminate the infection completely, one would theoretically regain the "healthy" status. But if you try to eliminate EBV in another subgroup of ME/CFS caused by another pathogen, you will not be able to cure the ME. It would only help to reduce the symptoms caused by reactivations of that virus due to immunosuppression. That is to say, in those patients who do not have HLA-II alleles susceptible to EBV but who have developed MS caused by another pathogen and end up having problems with EBV due to immunosuppression, eliminating the pathogen causing the disease with some treatment would allow EBV to be controlled again since it does not present these susceptibility alleles.

Knowing which HLA-II alleles you have can help you to know if you belong to the EBV subgroup. Although this is what we have to check in the study with patients.

 

[Pyrrhus]

EBV is a very clever virus and takes advantage of the increase in IFN-γ produced during the antiviral response to infect new cells. Since IFN-γ enhances the immune response by increasing the expression of MHC-II in cells so that they present more antigens. This increase in MHC-II is exploited by EBV to infect new cells through gp42-MHCII interaction that previously did not express it.

This sounds like one of the ways that infection with a non-herpesvirus can lead to a re-activation of EBV?

 

[godlovesatrier]

Really wish there was an autovaccine or the like for ebv. Can't believe we have to wait 5 years for the moderna vaccine

It's a very clever virus. Doesn't matter what I do it seems to come back. Also I think the antiviral angle is dead on. All it does is contain the levels. But what I've noticed is as soon as you get a vaccine they all reactivate. So one single event sets you right back.

 

[Rufous McKinney]

But what I've noticed is as soon as you get a vaccine they all reactivate. So one single event sets you right back.

my husband's got a mysterious staph infection some years ago (walking on a beach, do not walk barefoot on beaches)

It reactivated after his J and J shot, and the whole lower arm went off/ had to get antiobiotics.

now of course the ER doctor indicated this had nothing to do with getting vaccinated. But we know better