There has been a lot of questions about how a retroviral model would fit in to the world of ME/CFS lately. Could it be responsible in outbreak situations and could it go into remission from time to time, and what would be the mode of transmission if it does both of those?
I've been laying here in 'flare up' misery for a couple of weeks now and my brain has been stirring the pot on those very questions. Considering the fact that I don't have a PhD in Microbiology and I am in the middle of flare take what my brain has come up with, with a large dose of salt. (grins) Now that the caveat is out of the way, forward ho.
First of all let's revisit transmission. We know for a fact that somewhere in the vicinity of 3% of the worlds population is infected with XMRV. [1, 2] Doing the math that means somewhere in the neighborhood of 200 million infected people, of the 200 million infected 17 million or about 8.5% are diagnosed with ME/CFS. Some of us are from outbreaks that are known and reported. Some of us consider ourselves to not be part of the outbreak set. I'm not sure this is true. I know I about fell on the floor when I read that the San Antonio, Texas area had an outbreak between 1970 and 1973.  That doesn't come up in many places in the well known literature. So how would someone know if their area had an outbreak and how would someone know if there was an outbreak until 1. well after the fact and 2. if and only if a doctor reports it and it gets written down somewhere and that somewhere gets brought to your attention in reading material. In other words a lot of planets would have to align to really know if you are part of outbreak or not.
So what are the percentages of people actually affected in a cluster outbreak? If say 3 percent of the population of an area were affected that would argue for a direct correlation. And if only 8.5% of the XMRV infected actually end up with ME/CFS then one might make the correlation between percent infected and the percent of those who have some other factor (other than XMRV) that translates from XMRV to ME/CFS. It does make you go hmmm, what else is involved?
My blurry brain says it might look something like this;
XMRV infection (age) + Stress/Cortisol production over life time + Hormone levels/Androgen production specific to individual + Number of Viral infections in lifetime = Sever/Moderate/Light ME/CFS
Which goes back to transmission. When did the person or persons become infected? At birth, this would argue well for the school outbreaks as children tend to be born in clusters. Ever notice how you see one pregnant woman and all the sudden there are twenty more. (grins) If a percent of the women in a town or community are infected then they have a 50% to 75% percent chance of passing it directly to the child  and then add to the chance of passing it on via breast milk which adds another 18% 
Transmission can happen as a result of blood products used during child hood illness and accidents or later as young people mature and become sexually active. When ever you get the bug it begins the work of replicating.
Replication of a retrovirus is the period when you are most likely to feel or experience symptoms. This is when the virus which is already inserted into a cell will make a copy of itself, release that copy and that copy will go and infect another cell. During this period a lot of things can happen. XMRV can make partial copies and be stopped from complete replication by antiviral mechanisms like APOBEC's, TRIM's [5,6] and RNAse L cellular antiviral protections that are part of our cellular and lymphatic systems. Believe it or not this is actually bad. (grin) partial proteins that get pushed out of the cell and into the system can reek a lot of havoc 
For instance, causing an over abundance of certain proteins may make the body stop producing your own version of that protein however the viral protein may not be useable by the body so you end up with a deficit of a particular protein. Viral use of a set of protein building blocks can lead to a reduction of building blocks for other things that the body needs causing a depletion of what would normally use the blocks being used by the virus. The body may try to overcompensate and dump large amounts of a particular protein or building block causing the system to have to work overtime to utilized these building blocks causing problems and back ups in the system. Then there are the building blocks or viral made proteins that get hung out there and reek havoc just by being the wrong thing in the wrong place at the wrong time.
So what caused the virus to replicate in the first place? Well, Reeves and company might have got a small piece of the puzzle right, (hey easy with the rotten tomatoes there) stress or cortisol is a major stimulant for XMRV. The more stress in childhood the more XMRV that is made the more cells that are infected along the way. Stress in childhood is likely a predictor of who may end up with full blown ME/CFS in that the amount of cortisol produced in the younger years may lead to an earlier onset and a higher viral load later on. In addition type A personalities produce higher levels or cortisol on a regular basis which could account for the larger percentage of type A people with the illness.
The other factor is androgen production.  Men who produce large amounts of testosterone and women who produce large amounts of estrogen are going to need a higher androgen production and hence are more likely if they have XMRV at higher levels. Women who have an earlier onset of puberty may experience higher viral loads as well. Add in the amounts of hormones that women produce on a monthly basis into the replication mix.
In addition to these two replication stimulants there may be (or not) a tendency of XMRV to act in the way that other MLV do and recombine with other MLV's. The replication patterns of other MLV's may be diffrent than XMRV adding yet another possible replication method to the mix. And of course there may well be a problem with oEstrogens which are in all petroleum based products from plastics to medications to foods.
If XMRV is replicating based on cortisol and androgens then some people are going to build up faster when looking at the factors, and slower in others based on the combination. So within a community or group there will be a percentage of persons infected, a percentage of persons who have reached a critical load of XMRV in the system that the bodies antivirals are working hard to keep in check. For the most part without the stimulation from androgens and cortisol the XMRV virus is dormant replicating only in cells that replicate to replace themselves.
Along comes two triggering factors, factor A is the introduction of another virus that takes the bodies systems attention away from XMRV. Factor B is either an androgen spike or cortisol spike and voila you now have a tilted system in favor of XMRV replication and that replication dumps proteins and partial viral strings into the system as your body and the virus duke it out. This is the "outbreak" group. This is the group of people who develop ME/CFS anytime a major virus sweeps through a community. It could be one or two and it could be twenty or thirty with no one really the wiser for it.
However, when you have outbreaks that affect 200 to 500 people or a group of children or a group of nuns then it gets peoples attention. Especially since this is not the usual needle using, risky sex behavior group of people. What was not understood and is only now being seen, is the fact that a very large group of people actually have the virus. (200 million people is nothing to sneeze at) That this retrovirus has been in the population for at least 100 years and that of the group of XMRV infected at least .085% of them will develop ME/CFS either now or at some point in the future.
So what about remission? Can the body actually provide a remission from XMRV? It's quite possible that viral loads can be reduced over a long period of time or a short period of time. Remember two facts. One that XMRV is more or less dormant unless stimulated and that the production of partial virus is what is so hard on the system. On the short period if you have a hard hit of, say, cortisol and/or androgen and an outside virus hits the system, you may get sick short term. If you have a very healthy immune system the hit will come (the worst flu of your life) and go. It may be possible to beat the XMRV back in a short period of time say 6 months to a year, case in point my ex husband became ill and struggled for about a year, then recovered however, not to pre illness levels. However, even if you manage to beat it at the time, the potential to develop full blown ME/CFS is still there. Type B personalities or those with low hormone production are much more likely than a type A personality with more, say testosterone production to be able to beat the virus short term.
So what would have to happen in order to beat this retrovirus in the long term or to experience a remission. For about 20% there is nothing that can be done short of drug intervention. These are the sickest of us who may have low immune systems to begin with and then may have either a constant cortisol production or a level of hormone production that is higher than average. Whatever the factors involved, the system of some patients can not recover on their own.
For the lightly or moderately affected the possibility of recovery may be possible but there are layers that have to be dealt with and each persons layers are different. First you have androgen and cortisol levels that would have to regulated and then layer on top of that problems brought on by protein and partial viral strings that get caught in the system. Those viral strings and proteins begin creating chemical sensitivities and other intolerances. The first layer that has to be delt with before the deeper problems caused by a retrovirus can be addressed if you don't have access to antiretroviral drugs and other drug thearapys. In fact each of us has quite a solar system of planets that will have to align in order to get a remission. The list may look something like this;
1.viral proteins that are causing problems such as celiac disease, mold intolerance and chemical sensitivities have to be address by avoidance most likely for a lifetime or at least until a complete remission.
2. removing outside viral and bacterial hits to the systems. (Course it's hard to ask the spouse to decontaminate upon entering the sterile house and sending the children to boarding school while you get better is kinda hard on the family.) Hopefully antivirals and antibiotics can help to counteract some of the problem but getting these treatments right now is difficult.
3. Revamp your entire personality. If you were a type A or are a "worrier" then you will have to retrain your entire mental and physical system to a type B personality in order to reduce cortisol production on a daily level. And you can never go back to being a type A personality or pushing your system in any way that ups the production of cortisol.
4. anti-hormone products. Which of course will mess with your system in other ways but will reduce XMRV production. (grins)
5. Listen to your body and do what it says. But be able to sort out what is fear from the brain and what is really body signals. Not easy sometimes but doable.
Complete these 5 steps and you could go into a remission and even stay in remission for a good long time. If you have a combination of a few of these steps plus a good immune system remission could happen a lot faster. Most of the anecdotal accounts of remission that I've read have been a combination of taking very good care of the self including giving up the type A way of life and a good immune system or immune boosters.
The take home message in all of this? Yes a retroviral model works for outbreaks and remissions. But there still is no cure or treatment. Until the medical establishment understands this illness as well as we do then there will be no treatment protocols that help us even get to the remission status. Oh, wait we knew all that before. (grins)
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1. Polygenic Pathways, -
PDF (299.1 KB) Document Type:Manuscript
Date:Received 15 July 2010 01:56 UTC; Posted 15 July 2010
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Transmission, Remission and Outbreaks, Oh My!
Blog entry posted by George, Aug 16, 2010.