FDA and NIH confirm WPI XMRV findings (report of leaked presentation)

[judderwocky]

ok... but thats just one stress hormone.... you're forgetting things like adrenaline... which are known to impact immune function... cortisol from my understanding is a long term stress hormone... something your body produces after having been stressed for a while... there are other hormones that can be released in the short term that would theoretically also have an effect on the replication of the virus... then after you have an initial cluster of the virus in a group of cells, the increases in stress cause the virus to explode even further....

also im curious as to how they studied cortisol in patients before they had cfs... did they have blood in storage prior to onset? and if so was the blood being studied as part of another disease cohort? what about while it was happening? a lot of people don't seek treatment immediately

i know i was stressed when it happened. i was also dieting.

even apart from cortisol... stress affects a number of innate defense pathways which can allow for higher replication simply because cells are more vulnerable... even other retroviruses are more susceptible to transmission to individuals that have poor diet and smoke... because these things decrease the innate immunity of the viable cells....

i'm not saying its the only cause...my guess is that there is a cluster of factors...stress being one of them... but obviously genetics would contribute as well...

just my two cents.

 

[SunnyGal]

My entire life, any time I was stressed I had CFS symptoms flare up. Once the stress passed I would recover my health to my pre-stress levels. But I was never even close to being diagnosable as having CFS until I had undergone intense stress for a prolonged period of time. During that time I clearly had high cortisol (dragging all day then feeling best in the evenings/night). It is my belief that cortisol (among who knows what else) played a role in activating XMRV in my body, leading to my developing full-blown CFS. Unlike the rest of my life, once tihs period of stress passed I did not recover to my pre-stress level of health.

Another possible scenario is that people are carrying XMRV but it's largely inactive, they then contract some infection (EBV, Lyme, whatever), which causes cortisol to go up, which in turn activates XMRV, potentially tripping them into CFS.

Sunny

 

[judderwocky]

im not saying the stress caused it... but i feel like i made myself susceptible... i dont know... i took a lot of counseling classes in college... sometimes i honestly wonder if i just haven't internalized some of the blame people put on CFS and am looking for things i did my life to cause it ... meh...

interesting the tulane presentation is up on the other thread and it has some really new interesting stuff on affected cell lines also... they have cool green slides of infected xmrv cells ;p

 

[julius]

actually low cortisol is more common in CFS.

High cortisol tends to show up more in depression/anxiety disorders.

 

[Daffodil]

when dr. alter said they found "XMRV and related viruses" ...he just meant different strains...

 

[SunnyGal]

You have to keep in mind that stress doesn't mean just feeling emotional stress. Stresses on the body include physical stresses, such as an infection or chemical/mold exposure, among other things. I do not have an acute onset CFS, where I got sick and then never recovered. I had work-related stress that preceeded my illness. But, with acute onset CFS the illness/infection that preceeds CFS is also a stress and also causes high cortisol.

Yes, most with CFS have low cortisol but it may well be that they had high cortisol at the beginning of their illness, in the first weeks or months, when they wouldn't have known they weren't going to recover. No one checks cortisol levels at that point.

It may be that XMRV is activated in the beginning by high cortisol, the immune system is then compromised and other infections, also known to be immunosuppressant, take hold, and then you're unable to recover. The adrenals can only sustain a high level of cortisol (used to address infections) for awhile and when when the immune system is unable to clear the infections the adrenals eventually give out, and cortisol then goes low as we see in most PWC. But an initial stress (infection, emotional stress, chemical or mold exposure) may have caused the high cortisol which activated XMRV in the first place.

 

[Stone]

Would anyone care to venture a semi-educated guess (as far as that is possible) as to when, hypothetically speaking, a child who was born with XMRV might have enough of the virus to be detected by the (soon to be available) XMRV test? How old might a well child need to be before he/she might have a high enough viral load to be detected, assuming the child is actually XMRV infected? Just something I'm kicking around in my mind. It might not be knowable at this juncture, but I'm just wondering if anyone might want to hypothesize about it.

 

[George]

Hi Stone and All

Would anyone care to venture a semi-educated guess (as far as that is possible) as to when, hypothetically speaking, a child who was born with XMRV might have enough of the virus to be detected by the (soon to be available) XMRV test? How old might a well child need to be before he/she might have a high enough viral load to be detected, assuming the child is actually XMRV infected? Just something I'm kicking around in my mind. It might not be knowable at this juncture, but I'm just wondering if anyone might want to hypothesize about it.

I just finished the Dr.'s Rusecetti's presentations and the mechanism looks like it will be more complicated than a straight viral infect which hit's a "load" level and then you have CFS onset. If I'm following this correctly the XMRV may need to combine with another virus in order for it to begin making certain viral proteins that are associated with actual illness.

For instance a person could have CFS onset anywhere from age 11 to age 50 depending on when certain other MLV and/or other virus recombines in order to create a new protein producing viral recombination that actually creates CFS. That's not a proven fact but that's what both of the Dr.'s Rusecetti are working on right now and that's based on best model's found in mice.

So anyone carrying the XMRV virus at high loads anyway but, it's a slow replicator, (thank goodness) would also have to be hit with an additional MLV most likely another polytropic or PMLV or another xenotropic XMLV in order to create illness. These other MLV's could come from vaccines that use MLV's that are known to be harmless to humans by themselves. I've never subscribed to the vaccine theory because in order for it to work nearly everyone would have to have onset after a vaccine. Current rate of vaccine onset is only 3%. I know my onset was after a viral infection (EBV) not vaccination, but vaccinations could introduce other MLV's that may need to reproduce to certain levels in order to be able to recombine with XMRV and or an additional virus like EBV or other that would cause the actual mutatogenisis to take place.

It will be awhile until we know if that is in fact the pathogenesis for CFS, but it's good that they are working on finding the pathogenesis, that's been kind of an abandon field.

What drives me crazy is they still don't know where the main reservoir for the virus is located. GACKKKK. But nobody is looking in lymph tissue or bone marrow or spinal fluid yet so we'll see.

I am so going to pay for being up this late on the marrow!

 

[judderwocky]

thats the other thing... the lower cortisol levels later on could be indicative of deficiency... so many hormones get depleted from chronic illness... yet retroviruses respond to most hormones that cause cell differentiation... at least thats my understanding... so increasing activity, doing exercise... things that involve stressors end up causing the virus to shed more readily, and cell that is being "washed" by these hormones is more susceptible... like prostate cells because of all the androgens... i dont know if cortisol would cassify in this group of hormones or not... i know it depresses some immune functions, but i think it also stimulates white blood cells... at least initially.... i know that in a hospital they will tell you a high white blood cell count can be stress related and doesn't always signal an infection.... if something can cause cell differentiation, id say there is a good chance that its going to at least impact viral shedding.... but thats just a hunch.... i can't really base it off a study

i just know that a lot of hormones... even seemingly innocuous ones like vitamin d, influence viral sheding in a lot of these... i mean, even cell to cell signaling pathways can spur viral shedding... just being in contact with other cells can cause additional shedding in some....

 

[caledonia]

Does anyone know if the XMRV testing is picking up on all the strains of XMRV or just one?

 

[thegodofpleasure]

Speculation on disease mechanisms.

Hi George,

Have a look at this thread - it's very relevant to what you have been talking about, re the disease mechanism !

http://www.forums.aboutmecfs.org/sh...ot-Recipe-for-Disease-A-Gene-and-a-Virus-quot

What drives me crazy is they still don't know where the main reservoir for the virus is located. GACKKKK. But nobody is looking in lymph tissue or bone marrow or spinal fluid yet so we'll see.

In my view, whilst publicly, we aren't yet aware of what is being done, I am confident that they are looking all over the place for the reservoirs of the virus in humans. Dr. Eric Klein (Cleveland Clinic) talked recently about the research work that has already been done on prmates, to this end.
Sad, but necessary IMO

http://webcasts.prous.com/netadmin/...e7O0caInZp8x1BlrXwMxuZNZiIYeq9qt7xhfYJFaWzg==

With regards to the discussion of cortisol levels, it is my understanding that a dysregulated HPA (hypothalamus - pituitary axis) is thought to be the cause of low cortisol in ME/CFS. Hence, in terms of an XMRV model of disease, I suspect that the HPA will be found to be infected and thus damaged in some way.

Regards,

TGOP

 

[usedtobeperkytina]

Further to that comment: There is also no objective evidence of increased stress (as measured by cortisol levels) in patients prior to onset, at onset, or immediately after onset. The increased cortisol is only found in patients who have been sick for a while (at least six months I think, and only in some of them). Therefore, the most likely explanation is that the serious stress from just having the disease is the cause of the higher cortisol findings. IOW, raised cortisol is a secondary consequence of having ME or CFS, and is not associated with primary causation.

This is a serious problem for the stress genesis model. If there is no objective sign of stress prior to onset, at onset, or in the weeks and months immediately after onset, then how can it be a causal factor in onset, or the perpetuation of the symptoms (at least initially)?

Sean, from what I have heard from other patients, and my own experience, most of us have lower than normal cortisol after getting the disease.

Also, since testing is usually not done until after the person is ill, and by the way, the fatigue must be over six months to get a diagnosis, then of course there is not way of knowing whether the people had insreased cortisol. I am afraid all we have is anecdotal evidence.

I can say for me, stress was and is a factor. I do not believe it is caused by stress, but as Mikovits said, cortisol does make it rev up. That makes sense with the push and crash cycle. Plus, my symptoms (headache and nausea) are worse in times of stress.

Of course, I think co-infections may play a role, androgen hormone fluctuations and other factors may be the trigger in some people. I thin for many of us, it is a combination of these triggers that may have pushed us over the edge, or down into the labyrinth, as it were.

Tina

 

[usedtobeperkytina]

If there is a replication after triggers, and then immune system response, and then another trigger, etc., as Mikovits said about needing to stop those triggers, then it would depend on the immune system of that child, but mostly what triggers they have, that is how many viruses they are exposed to, vaccines, and other hormones.

So, there wouldn't be a certain age where it would show up, it would be different, child to child.

Tina

 

[taniaaust1]

LOL! I'd be right there with you.

[Suddenly envisioning a huge mass of bow-tied, trench-coated ME/CFS patients "sneaking" into some poor innocent editor's office....]

They'd get caught.. probably some would fall asleep when they had to stop and rest. Hard to sneak, i walk into things. We'd be the worlds worst burglers.

 

[taniaaust1]

I shown many people the Dr. Oz, and they dont accept it. Until its on national TV, no one will take much notice. Sorry, I should have read it all before I posted, but it does give us an insight into what a small number of people feel.

nods.. im sooo frustrated right now at my boyfriend. i kept on telling him about what is going on here and he dont really believe it at all...so i ended up showing him it was in new scientist, so suddenly he's a bit more open to the whole idea. Frustrating as their sources was the same as mine.

There is going to be a completely different reaction to what there is now once it goes properly public and i think the CDC and the big organisations know that.

 

[taniaaust1]

So what are the other two negatives? Bridget Huber (at Tufts) and CDC, right?

the study our good friend Wessley was a part of was another of the negative studies...

 

[WADoll]

I may be getting totally ahead of myself here....
My concern may be the authorities enforce unproven treatments on anyone who is XMRV +ve. Especially if the infection rate is as high as recently quoted and the contagion is fairly transmissible.

 

[bullybeef]

I know this is may be a bit OTT, but if it was so transmissible, would it be conceivable that a quarantine order may come into effect?

 

[pollycbr125]

actually low cortisol is more common in CFS.

High cortisol tends to show up more in depression/anxiety disorders.

yeah my cortisol was on the low side YAY I knew i wasnt mad

 

[alex3619]

Hi bullybeef

How do you quarantine up to ten percent of the population? Many ME and CFS patients are quarantined anyway, being housebound, but how do you enforce that on all the rest of the infected? If it can be shown that most with XMRV are not infectious, but some are, tnen those who are infectious might be quarantined - but we are years away from that point at least. If everyone with XMRV were quarantined, the economic impact alone would cause a new global financial crisis, one with no end.

It is far more likely they will rush a vaccine, then mass vaccinate most of the world. This will stimulate the economy rather than crash it, but push government debts even higher.

Bye
Alex

I know this is may be a bit OTT, but if it was so transmissible, would it be conceivable that a quarantine order may come into effect?