XMRV Study No. 4

[Kati]

To the risk of repeating myself, I got an IgM+ (acute infection) EBV after a patient I was treating (for cancer) spit straight into my mouth while talking. This was in November 2008- I have only gotten worse since then.

 

[kurt]

My family all got CFS in the course of 3 months. We all caught something or something was activated at the same time. I am adopted so genetic susceptibility in our caseis not a good justification for the four of us to have sudden onset CFS.

A whole family including non-genetic relatives in 3 months? Just curious since you are in Mass, were you tested for Lyme? Or for Herpes? I have read we can lose our immunity to some herpes strains as adults and there can be cluster outbreaks like that, particularly of HHV6, but others also.

 

[Kati]

i think the acute phase isnt mono at all. its a mono-like illness which reactivates the EBV (or HHV6 or CMV) and thats why the initial tests say IgM+ for one or more of the herpes viruses.

HTLV and HIV cause a mono-like illness too during primary infection...right?

Interesting perspective Mandy, now could you come to my next dr appointment and explain that to my dr???

Another question, wouldn't the EBV Igm and Igg be specific for EBV???

 

[V99]

As the don't know too much about XMRV, they will be exploring every avenue. However, to say it could explain every case of CFS is unlikely, because it's a heterogeneous group. But we don't know much, so it may. The criteria will be crucial in determining this.

 

[garcia]

EXACTLY, there is little similarity between CFS and AIDS other than sharing re-activated herpes infections.

I'd beg to differ. The kind of immunosuppression we get is reminiscent of (though not exactly the same as) aids & end-stage cancer. Having had a mouth full of yeast at one stage, where I could feel it growing in real time until every surface was covered, convinced me of that.

And when an AIDS patient starts getting HHV6 or Mono activation guess what, they can get CFS too.

I thought this was very very rare. Do we have any documented cases of aids/cfs??

CAA is funding a study that has literally tracked mono patients and can separate those who will get CFS from those who will not based on their cytokine responses.

A better explanation is that whatever gives you CFS is there before you get mono, and that your cytokine response (from day 1) will reflect this. This isn't just a theoretical argument for me, but based on my own experience. As soon as I got mono/ebv, whatever it is that causes CFS was activated. I knew something was wrong from day 1. Not only that but I suspect the agent was there before mono/ebv since I was getting minor symptoms such as poor stress tolerance & unrefreshing sleep. I wasn't "sick" before EBV, but I wasn't fully "healthy" either.

Some people apparently do not manage chronic herpes activation well, and that gives them (us) CFS. Not XMRV.

IMHO you are confusing the effect with the cause. What makes us a poor manager of herpes infections? Retrovirus perhaps?

But herpes is pretty boring and saying CFS is caused by re-activated herpes and enteroviruses will not likely ever be reported in Science, just not very sensational.

You are right, it is boring! Boring because it has been looked at to death. If there is one hypothesis that has been given ample air-play in CFS it is chronic EBV. It just simply doesn't hold up.

People with severe CFS can often recover if they can tolerate the strong antivirals required to stop that virus.

If that were the case Montoya's follow up study would not have failed so spectacularly.

I think that reducing coinfections is a good idea and can help the body regain homoeostasis, and even recover. But this applies to all coinfections (not just viral). The same argument also applies to toxin-removal, where something like chelation can help you regain homoeostasis. Doesn't mean that the underlying cause was virus X, bacterium Y or toxin Z. Just that removing them helped your own body regain control of whatever was causing the CFS.

Also, raising glutathione levels stops herpes replication, probably one of the reason that methylation support helps many PWC so well.

It also stops retroviral replication I'd imagine. And reduces toxins. And stops bacterial infections. And rebalances neurotransmitters ....

Again, you are right on target. If you want to understand why XMRV is a poor causal hypothesis for CFS, just start with the epidemiology of CFS. It is nothing like the epidemiology of AIDS.

This argument does hold some water. But again it is a general argument and certainly not strong enough to completely eliminate any possibility.

IF you look at CFS history, particularly the outbreaks, it is clear that the infection vector is a combination of susceptible genetics or environmental preconditions, combined with airborne or food-borne viral exposure.

The problem with these kind of catch-all hypotheses is that they are very difficult to disprove. I mean how would you go about proving/disproving them? They also don't explain much. Maybe you are right and there is no neat single-cause explanation. Maybe it is just a multifactorial mess, and we will never have a neat solution. But that shouldn't stop us looking for one if we can find it.

 

[bakercape]

Tested for LYME

In respose to Kurts question about wondering if my family was tested for HHV-6 and Lyme. At the time we first became ill we were all treated for Lyme as a precation. It helped none of us. We were also living in MAine at the Time.I have been tested for Lyme 6 times using the commo Lyme test and Western Blot over the last 20 years and always been neg.

We were never tested for HHV_6 but were positive for ebv and had chicken pox at the same time in the initial months of our illness.Mom also had shingles while brother and I had EBV/Chicke Pox.

 

[Hip]

My family all got CFS in the course of 3 months. We all caught something or something was activated at the same time. I am adopted so genetic susceptibility in our caseis not a good justification for the four of us to have sudden onset CFS.

Bakercape, this may not be your case, but check out http://chronicsorethroat.wordpress.com/, which is about a potent little virus, that spreads easily within families, and can create CFS in people. However, if your symptoms don't match those described on the above site, then this is not your case.

Also, take a inspiration from the TV genius "Dr Gregory House", and perhaps do a little lateral thinking about causes. For example, if all 3 of you are living in the same place, consider toxic poisoning of the home as a possibility. Carbon monoxide poisoning from a fault heating system; spillage of toxic pesticides, etc in the garage (many garages are linked to the house, and air can circulate), toxic mold, etc. If you feel better when staying away at a hotel or at a friend's home, then this suggests there may be toxin in your home.

I hope this helps.

 

[bakercape]

Thanks

for the info fellow sufferers. I don;t have that symptomology Hip. No chronic sore throat.

I am hopeful XMRV can explain the chronic viral infections so many of us seem to display like EBV and Herpes Virus's. I'm not holding my breath though.

I do believe if XMRV proves to be transmitted exactly like HIV that it will not explain the outbreaks of CFS unfortunately.

Hopefully we will have our answers sooner rather than latter but you can't rush good science unfortunately. I wish someone could validate the Science paper using a different technique. Oh well I've waited 22 years I can wait another year or two for the truth on XMRV.

 

[kurt]

dr. mikovits, in her last seminar (i think) brought up the upcoming CDC studies....she wouldnt have done this if she didn't know there was some good news coming from them, right? i also found an article that says "According to CDC, their studies using samples obtained from the Whittemore Peterson Institute has HHS attention." so it seems the CDC probably found XMRV..!?

I believe the reason she brought that up was because she has hopes they will find XMRV. But that does not mean the CDC found XMRV. I have heard the testing is not even complete yet, so she could not know the outcome. After testing they have to go through all the write-up and peer review prior to publication, so that study will probably not be out for quite a few months still.

I'd beg to differ. The kind of immunosuppression we get is reminiscent of (though not exactly the same as) aids & end-stage cancer. Having had a mouth full of yeast at one stage, where I could feel it growing in real time until every surface was covered, convinced me of that.
A better explanation is that whatever gives you CFS is there before you get mono, and that your cytokine response (from day 1) will reflect this. This isn't just a theoretical argument for me, but based on my own experience. As soon as I got mono/ebv, whatever it is that causes CFS was activated. I knew something was wrong from day 1. Not only that but I suspect the agent was there before mono/ebv since I was getting minor symptoms such as poor stress tolerance & unrefreshing sleep. I wasn't "sick" before EBV, but I wasn't fully "healthy" either.
IMHO you are confusing the effect with the cause. What makes us a poor manager of herpes infections? Retrovirus perhaps?
You are right, it is boring! Boring because it has been looked at to death. If there is one hypothesis that has been given ample air-play in CFS it is chronic EBV. It just simply doesn't hold up.
If that were the case Montoya's follow up study would not have failed so spectacularly.
I think that reducing coinfections is a good idea and can help the body regain homoeostasis, and even recover. But this applies to all coinfections (not just viral). The same argument also applies to toxin-removal, where something like chelation can help you regain homoeostasis. Doesn't mean that the underlying cause was virus X, bacterium Y or toxin Z. Just that removing them helped your own body regain control of whatever was causing the CFS.
It also stops retroviral replication I'd imagine. And reduces toxins. And stops bacterial infections. And rebalances neurotransmitters ....
This argument does hold some water. But again it is a general argument and certainly not strong enough to completely eliminate any possibility.
The problem with these kind of catch-all hypotheses is that they are very difficult to disprove. I mean how would you go about proving/disproving them? They also don't explain much. Maybe you are right and there is no neat single-cause explanation. Maybe it is just a multifactorial mess, and we will never have a neat solution. But that shouldn't stop us looking for one if we can find it.

The immune profile of AIDS is different from that of CFS.

Could there be some underlying pre-infection in CFS that allows the herpes to cause so much harm? That makes sense. Is it XMRV? That seems unlikely given the epidemiology. But some other retrovirus, yes, maybe a HERV, or perhaps an enterovirus, toxins blocking metabolic processes, etc.

As for herpes, I believe the WPI virachip study gives us the answer, but again, it is sooo boring that even the researchers have not even mentioned it again after their early presentations. What the virachip study showed was multiple reactivated herpes infections, plus activated HERVs. Multiple herpes might include much more than EBV, add to that Zoster/ChickenPox, Roseola/Shingles (HHV6), even Herpes simplex and/or complex. I do not believe the WPI virachip tested for enteroviruses, but that is another candidate precursor infection.

Herpes does not re-activate in a healthy person generally, but it is possible, particularly HHV6 (aka Roseola). If you have lost your immunity and get re-exposed, or have high stress maybe a low glutathione levels for various reasons.

The second Montoya study failure does not mean no herpes, only that the drug did not work for that cohort.

I agree about homeostasis and believe the GD-MB hypothesis will eventually be proven important in that part of the puzzle.

And multifactorial cause, basically a spectrum disorder model, seems to me the only explanation for the diverse expression and research findings in CFS, I would love to find a silver bullet treatment for something like XMRV. However, I am a realist and just can not get past the obvious flaws with the XMRV hypothesis, starting with the epidemiology, then moving to the lack of CFS in presumed XMRV positive cohorts with prostate cancer, and then the problems with the Science article (inadequate control testing, calling MuLV antibodies XMRV antibodies, not revealing required re-testing, etc.), validation study problems, and then WPI's making too much of an early research finding. Most research groups would be far more tentative about such a new finding. There have been HUNDREDS of studies attempting to link retroviral cause with other diseases, most have failed due to HERVs or other reasons.

In respose to Kurts question about wondering if my family was tested for HHV-6 and Lyme. At the time we first became ill we were all treated for Lyme as a precation. It helped none of us. We were also living in MAine at the Time.I have been tested for Lyme 6 times using the commo Lyme test and Western Blot over the last 20 years and always been neg.
We were never tested for HHV_6 but were positive for ebv and had chicken pox at the same time in the initial months of our illness.Mom also had shingles while brother and I had EBV/Chicke Pox.

So multiple herpes co-infections, shingles (proof of HHV6 exposure), and suspected but unproven Lyme. That certainly fits at least part of the multifactorial model of CFS.

Incidentally, my case is somewhat similar, three members of my family are sick with CFS, although one is high-functioning, but two of us are disabled by CFS. And just before this happened we had a younger family member with chicken pox, and one with Roseola (a rash illness that probably was HHV6), and suspected Lyme (we were positive on one test but that lab has been discredited so hard to say). We lived in Texas when this happened, our area in Texas (San Antonio) had a Lyme/Mycoplasma/CFS outbreak problem, and the Lone Star Tick, and we had Tick bites.

for the info fellow sufferers. I don;t have that symptomology Hip. No chronic sore throat.
I am hopeful XMRV can explain the chronic viral infections so many of us seem to display like EBV and Herpes Virus's. I'm not holding my breath though.
I do believe if XMRV proves to be transmitted exactly like HIV that it will not explain the outbreaks of CFS unfortunately.
Hopefully we will have our answers sooner rather than latter but you can't rush good science unfortunately. I wish someone could validate the Science paper using a different technique. Oh well I've waited 22 years I can wait another year or two for the truth on XMRV.

Given the amount of activity right now in the research world (unprecedented for CFS) I believe we will have the answer about XMRV within a year. And maybe we will know much, much more, even if XMRV gets busted, there is a lot of good research going on right now in the CFS world.

 

[Gerwyn]

one virus can cause an apparently multfactorial condition as in aids .The internet is awash with the bredth of symptoms caused by the virus they overlap me/cfs almost exactly.The current oinion leans toward the idea that aids is in fact several illnesses with the same causative organism

The immune profile of aids is somewhat different mainly in cell apotosis but there are many similarities

Your argument re hervs If the conditions provoke herv activation as part of the intrinsic immune system then those conditions would promote xmrv into replicative mode.The instrinsic herv activation system however is retrovirus specific and is not activated by other viruses.Vaccines containing live viruses however have been shown to reactivate inserted viruses such as XMRV

I dont think that the reasons for JM,s statements are known but everyone is entitled to a belief in the matter.

I find your argument re the epidemiology a little difficult to understand I wonder if you could elaborate?

Your argument relating to the failed drug trial could equally well be applied to the failed uk studies of course They could not detect XMRV in that cohort

 

[Dr. Yes]

one virus can cause an apparently multfactorial condition as in aids .The internet is awash with the bredth of symptoms caused by the virus they overlap me/cfs almost exactly.The current oinion leans toward the idea that aids is in fact several illnesses with the same causative organism

I read that as "the current onion leans toward.."! Thought it must be some quaint Welsh expression.

(Please don't edit it Gerwyn! People will think I'm mad.)

 

[dancer]

I also read "the current onion" and tried to wrap my brain around what I figured was a poetic metaphor.
Hmmm.... peeling away the various layers of knowledge....?

 

[Gerwyn]

I read that as "the current onion leans toward.."! Thought it must be some quaint Welsh expression.

(Please don't edit it Gerwyn! People will think I'm mad.)

i told you my typing was total rubbish

 

[starryeyes]

With all the evidence suggesting XMRV is so hard to detect, I'm a bit worried that we'll end up having the opposite problem and will end up finding XMRV in healthy people.

CFS, only 4% of healthy controls that the WPI tested had XMRV.

 

[kurt]

one virus can cause an apparently multfactorial condition as in aids .The internet is awash with the bredth of symptoms caused by the virus they overlap me/cfs almost exactly.The current oinion leans toward the idea that aids is in fact several illnesses with the same causative organism
The immune profile of aids is somewhat different mainly in cell apotosis but there are many similarities
Your argument re hervs If the conditions provoke herv activation as part of the intrinsic immune system then those conditions would promote xmrv into replicative mode.The instrinsic herv activation system however is retrovirus specific and is not activated by other viruses.Vaccines containing live viruses however have been shown to reactivate inserted viruses such as XMRV
I dont think that the reasons for JM,s statements are known but everyone is entitled to a belief in the matter.
I find your argument re the epidemiology a little difficult to understand I wonder if you could elaborate?
Your argument relating to the failed drug trial could equally well be applied to the failed uk studies of course They could not detect XMRV in that cohort

current opinion is that AIDS is caused by HIV, leading to immune suppression, then opportunistic infections which create the major symptoms and lead to death.

CFS does have some symptom overlap because it also includes immune suppression (of NK cells and some others) but it is a also very different and far less deadly immune problem, and CFS generally does not lead to death the way AIDS can. Our opportunistic infections seem to be largely herpes viruses, re-activated HERVs, and enteroviruses. The original cause of the NK cell problem is certainly in need of explanation, but herpes can cause that and so can stress, the NK cell can get used up by persistent infection, and we can get caught in a vicious circle when these deplete glutathione if a person has the right SNPs for weak methylation, which nearly ALL ME/CFS patients do have. And even stress depletes glutathione which explains that rather contentious part of our pathology.

Certainly I agree that in theory it is possible a retrovirus could be responsible for the depressed NK cells, but so could a number of other factors.

Having known someone who died of AIDS and also read about symptoms online I see very little similarity between CFS and AIDS, no more than between AIDS and Cancer, or other serious illnesses.

The reason WPI even pursued this apparently was that Mikovitz is a cancer virus expert and knew about lymphomas in AIDS so when she heard that a small subset of Peterson's CFS patients had lymphomas, she said 'it must be a retrovirus.' Well, maybe for a few CFS patients that is true, but I don't see good evidence for the XMRV hypothesis beyond a limited cohort like that.

Also, if you read the CFS-HERV research at Tufts (Dr Huber), you will find that in fact HHV6, a virus, does activate HERV apparently in CFS patients, including the variety K18 which produces a superantigen (sAG) that floods us with cytokines. This same HERV is also implicated in MS.

As for my epidemiology argument, in order to explain the epidemiology of CFS with a retrovirus I believe WPI will have to find a new mechanism of transmission for retroviruses in general. That is basic research and might be difficult. Anyway, if you go with the AIDS model, blood exchange is generally required, so transmission is like an STD or through transfusion or dirty needles. And also vertical transmission is possible. This conflicts starkly with CFS epidemiology which includes large outbreaks of people who work together but have only casual contact, and smaller outbreaks such as in families or individuals who monogamous, and have no history of STD exposure for many generations (so no initial infection exposure for later vertical transmission), and are not drug users and have not had any transfusions. Most spouses/partners of CFS patients are not sick at all (with a few exceptions). That suggests CFS is not blood borne, but may involve some communicable factors that some people will be susceptible to. AIDS spouses/partners do get sick and even die. I don't know the statistics but just observation tells me there is far more partner infection from AIDS than from CFS. The AIDS epidemiology was one of the early clues to the nature of the virus. The CFS epidemiology also supplies clues, but they do not point to blood exchange. Rather CFS seems to be precipitated by a number of different airborne infections, toxin exposures, traumas and injuries, all of which can deplete cellular resources and possibly start a complex vicious cycle in a person's metabolism, and also cause neurological injuries that may contribute to dysautonomia. Thus CFS epidemiology and onset seems to me more similar to other complex multifactorial diseases with multiple triggers and genetic involvement, such as MS, Autism, autoimmune disease, Cystic Fibrosis, Chronic Lyme, Mold illness, post-war syndromes, etc.

I really do not agree that AIDS is almost the same as CFS in symptoms or pathophysiology. AIDS does not include dysautonomia, brain fog, systemic unrelenting fatigue unrelieved by rest, post-exertional malaise, mitochondria dysfunction, or a number of other pathologies of CFS, probably unless the AIDS patient also has CFS (now THAT would be bad luck!). AIDS does often include Candida problems, herpes reactivations, and some cancers found in CFS. But that is just one part of CFS and only in a subset of patients. Yes, there are some common elements, I agree there is some overlap between AIDS and CFS, just not enough to say a retrovirus is an obvious common element, particularly given the differences in epidemiology. My opinion.

 

[gu3vara]

I've been following this debate between you two for a few days now and I really can't decide who's wrong and who's right, you both have excellent arguments for and against the XMRV theory. As much as I would like to believe XMRV is the cause of all our problems, it just seems too good to be true. I'm quite sure my autoimmune disease (hashimoto), stress levels and poor life habits all played a role in my CFS.

But perhaps all that wouldn't matter unless you have the famous X factor, XMRV or something else.

 

[cfs since 1998]

CFS, only 4% of healthy controls that the WPI tested had XMRV.

I know but there could be false negatives? Let's hope not.

 

[Hope123]

The original cause of the NK cell problem is certainly in need of explanation, but herpes can cause that and so can stress, the NK cell can get used up by persistent infection, and we can get caught in a vicious circle when these deplete glutathione if a person has the right SNPs for weak methylation, which nearly ALL ME/CFS patients do have. And even stress depletes glutathione which explains that rather contentious part of our pathology.

Kurt, perhaps this belongs in another thread but I'd like to see the data behind this glutathione depletion hypothesis and your statement that "nearly ALL" patients have this. Rich Van K. has a lot of ideas about this but they seem mostly theory and based on some anecdotes. If you have a published article based on people, I'd like to see that. As far as I can tell, this theory is pretty weak when it comes to the empirical evidence for it.

 

[Gerwyn]

current opinion is that AIDS is caused by HIV, leading to immune suppression, then opportunistic infections which create the major symptoms and lead to death.

CFS does have some symptom overlap because it also includes immune suppression (of NK cells and some others) but it is a also very different and far less deadly immune problem, and CFS generally does not lead to death the way AIDS can. Our opportunistic infections seem to be largely herpes viruses, re-activated HERVs, and enteroviruses. The original cause of the NK cell problem is certainly in need of explanation, but herpes can cause that and so can stress, the NK cell can get used up by persistent infection, and we can get caught in a vicious circle when these deplete glutathione if a person has the right SNPs for weak methylation, which nearly ALL ME/CFS patients do have. And even stress depletes glutathione which explains that rather contentious part of our pathology.

Certainly I agree that in theory it is possible a retrovirus could be responsible for the depressed NK cells, but so could a number of other factors.

Having known someone who died of AIDS and also read about symptoms online I see very little similarity between CFS and AIDS, no more than between AIDS and Cancer, or other serious illnesses.

The reason WPI even pursued this apparently was that Mikovitz is a cancer virus expert and knew about lymphomas in AIDS so when she heard that a small subset of Peterson's CFS patients had lymphomas, she said 'it must be a retrovirus.' Well, maybe for a few CFS patients that is true, but I don't see good evidence for the XMRV hypothesis beyond a limited cohort like that.

Also, if you read the CFS-HERV research at Tufts (Dr Huber), you will find that in fact HHV6, a virus, does activate HERV apparently in CFS patients, including the variety K18 which produces a superantigen (sAG) that floods us with cytokines. This same HERV is also implicated in MS.

As for my epidemiology argument, in order to explain the epidemiology of CFS with a retrovirus I believe WPI will have to find a new mechanism of transmission for retroviruses in general. That is basic research and might be difficult. Anyway, if you go with the AIDS model, blood exchange is generally required, so transmission is like an STD or through transfusion or dirty needles. And also vertical transmission is possible. This conflicts starkly with CFS epidemiology which includes large outbreaks of people who work together but have only casual contact, and smaller outbreaks such as in families or individuals who monogamous, and have no history of STD exposure for many generations (so no initial infection exposure for later vertical transmission), and are not drug users and have not had any transfusions. Most spouses/partners of CFS patients are not sick at all (with a few exceptions). That suggests CFS is not blood borne, but may involve some communicable factors that some people will be susceptible to. AIDS spouses/partners do get sick and even die. I don't know the statistics but just observation tells me there is far more partner infection from AIDS than from CFS. The AIDS epidemiology was one of the early clues to the nature of the virus. The CFS epidemiology also supplies clues, but they do not point to blood exchange. Rather CFS seems to be precipitated by a number of different airborne infections, toxin exposures, traumas and injuries, all of which can deplete cellular resources and possibly start a complex vicious cycle in a person's metabolism, and also cause neurological injuries that may contribute to dysautonomia. Thus CFS epidemiology and onset seems to me more similar to other complex multifactorial diseases with multiple triggers and genetic involvement, such as MS, Autism, autoimmune disease, Cystic Fibrosis, Chronic Lyme, Mold illness, post-war syndromes, etc.

I really do not agree that AIDS is almost the same as CFS in symptoms or pathophysiology. AIDS does not include dysautonomia, brain fog, systemic unrelenting fatigue unrelieved by rest, post-exertional malaise, mitochondria dysfunction, or a number of other pathologies of CFS, probably unless the AIDS patient also has CFS (now THAT would be bad luck!). AIDS does often include Candida problems, herpes reactivations, and some cancers found in CFS. But that is just one part of CFS and only in a subset of patients. Yes, there are some common elements, I agree there is some overlap between AIDS and CFS, just not enough to say a retrovirus is an obvious common element, particularly given the differences in epidemiology. My opinion.

I agree that the likelyhood of XMRV transmission via blood is very unlikely.That is why the studies looking for XMRV in whole blood samples were of such niave design





I know of some ME type outbreaks which could have had a viral cause but none for CFS

I dont know how you would establish monogomy for so many generations combined with premarital celibacy

XMRV is a gammaretrovirus which can be transmitted horizontally or host host droplet saliva sexual contact and so on--I dont see the need for a new model for transmission here

You would expect a herv to be activated by a latent virus like HHV-6 becoming active because of the association between interferon and cytokines.This is different from a herv becoming activated by an exogenous infection which is retroviral specific

I note that Huber has no problem with CFS being caused by a single virus. The paper claimed that the CFS in the patients had been caused by EBV though,

Unfortunately when measured objectively the herv activated in MS is not activated by HHV-6 Even though the Herv is indeed expressed there is no sign of HHV-6 either inserted or replicating Guiseppe et al Jen Vir 2007

 

[kurt]

Kurt, perhaps this belongs in another thread but I'd like to see the data behind this glutathione depletion hypothesis and your statement that "nearly ALL" patients have this. Rich Van K. has a lot of ideas about this but they seem mostly theory and based on some anecdotes. If you have a published article based on people, I'd like to see that. As far as I can tell, this theory is pretty weak when it comes to the empirical evidence for it.

Rich posted some results of genetic testing in a group of about 25 CFS patients once on another forum. They almost all had a narrow group of SNPs indicating a weak methylation system that could become blocked leading to glutathione depletion. That was what I was referring to with 'nearly ALL patients', bad genes for methylation. But there are a few exceptions. This theory is pretty strong as a centerpiece that ties together multiple research directions in my opinion, and I am surprised it has not made more headway. There have been a few limited papers and one presentation of a clinical study that had positive outcomes. The only problem I see with the hypothesis is that Rich emphasizes the methylation cycle block problems, and does not really address the multifactorial nature of the glutathione depletions very often. I suppose that is because there is so much other research into the causes of oxidative stress in CFS, he is probably addressing the area of greatest need. Anyway, here is a pub on the most recent clinical treatment study:

http://aboutmecfs.org/Trt/TrtMethylStudy09.pdf

The reason I refer to this often is that this helps tie everything together so neatly, particularly given that stress, trauma, flu-type illnesses, herpes re-activation, Lyme, mold, toxins, adrenal looping, most of the known triggers of CFS will contribute to glutathione depletion. So solutions would involve identifying and solving the factors of glutathione depletion, treating each person's combination of triggers/depleters, as well as unblocking the methylation cycle.

I know of some ME type outbreaks which could have had a viral cause but none for CFS
I dont know how you would establish monogomy for so many generations combined with premarital celibacy
XMRV is a gammaretrovirus which can be transmitted horizontally or host host droplet saliva sexual contact and so on--I dont see the need for a new model for transmission here
Unfortunately when measured objectively the herv activated in MS is not activated by HHV-6 Even though the Herv is indeed expressed there is no sign of HHV-6 either inserted or replicating Guiseppe et al Jen Vir 2007

CFS is ME, the CDC simply wanted a new name. We don't have different diseases, the expression is identical, diseases don't carry flags. Maybe you mean no viral trigger for CF, which may be true, I have not looked into that. In the UK CF is lumped in with ME which is unfortunate, but please do not lump in CFS with CF, just not even close to the same thing. Anyway outbreaks of ME/CFS in the US, Canada, Au, etc., have often followed a bad flu-like illness that goes around first.

Celibacy followed by monogamy for many generations is possible to establish in some isolated religious culture groups in the US that have CFS in modern group members but not in ancestors. That contradicts the vertical transmission vector or STD transmission hypothesis for XMRV. But you do have to know the family history to establish this.

Transmission mechanism of XMRV is unknown per Mikovitz so I don't know where you get the idea that it is transmitted horizontally or saliva, etc., and no new model is needed. That is an assumption. In an AIDS type model the transmission is blood and that is well established for that type of retrovirus, how would a gammaretrovirus be different? Particularly given the ultra low viral load in the blood I honestly can't see how XMRV might be transmitted at all, except maybe in an early infectious period.

I don't know which MS HERV you are referring to, there have been several mentioned in the literature, I am only familiar with K18 and my comment about HHV6 was specific to that, for CFS.