• Phoenix Rising needs funds to operate: please consider donating to support PR

Is there a connection between XMRV and HHV-6/7

anciendaze

Senior Member
Messages
1,841
Likes
4,790
I've just skimmed this thread, and might have missed something, but I think there is another way this tricky rascal of a virus can operate which causes endless confusion. Consider this a conspiracy theory which blames the virus for deliberately misleading both immune system and doctors.

First, there is plenty of reason to believe XMRV is active at some times and not others in infected people. There are also stages to the trainwreck of immune problems. I have not had a fever in about 15 years, where these were common at the beginning.

The most important characteristic I've gleaned from information about the virus itself is the connection with the RNase-L 2,5A pathway. This has a very specific function in controlling latent viral infections, where infected cells cannot be eliminated, but the virus can be destroyed, when it reappears, by an enzyme cleaving RNA. Clearly, inhibiting this helps an RNA virus like XMRV survive and propagate.

Aside from inserting genes and making copies of itself, at a low rate, and protecting itself, there doesn't seem to be much that XMRV by itself actually does. For survival it is best not to draw much attention to itself. Because the genes have been completely sequenced, we know there is not a lot of extra functionality hiding inside its genome.

The confusion I suspect in different kinds of onset comes from two sources. One is that this, like many, many infectious diseases, produces a spectrum of illness. At one extreme, we have people infected, but completely asymptomatic. (They may outnumber people with symptoms.) At the other extreme, we have people felled quickly by "the worst flu of my life" who know the day their illness began. In between we can expect to have a continuum of responses.

The second source of confusion is that the illness which catches our attention may not be the original XMRV infection. We may start out asymptomatic, then develop symptoms when a different infection stresses the specifically weakened immune pathways activated to fight it.

My own suspicion here is that this is the connection with vaccination. I tend to doubt the vaccine itself carries the virus. There are already too many available routes of transmission to require that assumption, and the times when people are vaccinated tend to occur when exposure to those is greatest. What I'm guessing is that the immunization exposes a defect previously introduced by XMRV.

Finally, here is something which might be more original, the infection which catches our attention could easily be an earlier viral infection which was driven into latency by a healthy immune system, then reactivated when XMRV crippled defense against latent viruses.

My own experience involved quarantine because of an outbreak of German measles. I was diagnosed as having this because of the classic signs of disease, plus the fact I had had a solid case of ordinary measles as a child. Textbooks say one such case confers life-long immunity.

The catch here is that part of the differential diagnosis of ordinary measles (rubeola) vs. German measles (rubella) is sensitivity to light (photophobia). I definitely had that while quarantined. This leads to two possibilities: my original case of measles as a child was misdiagnosed; the case of German measles was misdiagnosed, and my original latent measles infection was reactivated. Until I read about XMRV, that episode was an unexplainable anomaly.

If that could happen in one case, there is room for enormous confusion in others. This would be part of the reason few seem to agree about the relation to infectious disease.
 

Bob

Senior Member
Messages
16,455
Likes
34,047
Location
England (south coast)
I've just been reading about research which suggests that HHV-6 actively speeds up HIV replication, causing HIV infection to progress to AIDS more quickly.
So I wonder if HHV-6 might relate to XMRV in a similar way (i.e. infection with XMRV + HHV-6 = more likelihood of having ME/CFS) ?

It has also been suggested (by Huber) that HHV-6 can activate EBV which in turn can activate HERVs, which she suggests might cause ME/CFS symptoms.
Huber has suggested that HERVs may cause a subset of ME/CFS, but I think that members of this forum have pointed out perceived flaws in Huber's.

There may well be an interaction between Herpes viruses, HERVs, XMRV and other pathogens that haven't been worked out yet in people with ME/CFS...
Maybe it all revolves around XMRV, or maybe it is more subtle or more complex than that.

What does seem to be happening is that there seem to be many different pathogens, and some genes, involved at some level in some way.

Something to note is that HERVs are related to MLVs which are related to XMRV... So these similar genetic codes seem to be cropping up a lot with ME/CFS. I wonder if there is an interplay, or a reaction, between HERVs and XMRV in relation to ME/CFS, and if any other MLVs are involved.
 

muffin

Senior Member
Messages
940
Likes
15
HHV6 and HHV 7 are old theories but do have merit (to the brainless one here): From 1998, see below. Google HHV6 and Valtex and tons come up. Must say that I do think the Valtrex I have been on for two months has been helpful. More energy it seems. Brain still damaged.

Persistent Active Human Herpesvirus Six (Hhv-6) Infections In Patients With Chronic Fatigue Syndrome.Konstance K Knox, Ph.D.; Joseph H. Brewer, M.D. and Donald R. Carrigan, Ph.D. Institute for Viral Pathogenesis and Wisconsin Viral Research Group; Milwaukee, Wisconsin1 and St. Luke's Hospital; Kansas City, Missouri.

OBJECTIVE: Data from a number of laboratories have suggested a role for HHV-6 in the pathogenesis of chronic fatigue syndrome (CFS). In the studies described here we sought to explicitly test the hypothesis that a portion of patients with CFS have persistent, active HHV-6 infections.

METHODS: Blood samples from patients with CFS were evaluated by a rapid HHV-6 culture procedure. This technique diagnoses active HHV-6 infections by detecting transfer of the virus from the patient's blood leukocytes to a target human cell line. CFS patients from two CFS oriented clinics, a large infectious disease practice, and blood samples from CFS patients submitted to our laboratory from physicians and clinics around the United States were studied. Clinical characteristics of and multiple blood samples from a group of CFS patients from the infectious disease practice were evaluated in detail.

RESULTS: The cross-sectional (one blood sample per patient) incidence of active HHV-6 infection was 37% (128/349) in the CFS patients with the incidence being similar at all four sources of samples (range 25% to 47%). This incidence of active HHV-6 infection was significantly higher than the 0% seen in 26 normal controls (p<0.05).

To assess the possibility that HHV-6 infections may be episodic or variable with respect to viral load in patients with CFS, seven patients whose first blood samples were negative for active HHV-6 infection were retested at intervals ranging from 4 to 12 weeks after the initial sample was obtained. Three of the seven patients (43%) were found to be positive for active HHV-6 infection with the second sample. This finding suggested that active HHV-6 infections may be intermittently detectable in patients with CFS. This possibility was examined by testing at least four blood samples from each of four patients with CFS over periods of time ranging from 1 to 5 months. The consecutive blood samples from the four patients were found to be HHV-6 positive 58% (22/38) of the time with the positivity rates for the individual patients ranging from 40% (4/10) to 69% (9/13). These observations suggest that the active HHV-6 infections in patients with CFS are either intermittent or variable with respect to their viral load. Thus, an individual patient's HHV-6 infection status must be assessed using multiple blood samples obtained over a period of weeks or months. Also, the 37% estimate of the incidence of active HHV-6 infections in patients with CFS should be held as a minimal value since the true incidence may be higher (60% to 70%).

In the course of these studies it was observed that many HHV-6 positive CFS patients had central nervous system (CNS) involvement in their disease. To formally address this, 25 patients with CNS disease (abnormal SPECT or MRI scans, sensory abnormalities, cognitive defects, etc.) seen in the infectious disease practice were evaluated for active HHV-6 infections. Fourteen of the 25 patients (56%) were HHV-6 positive. This incidence of HHV-6 infection was higher (p < 0.08) than that seen in total population of unselected CFS patients (37%) suggesting that the selection for CFS with CNS involvement coselected for active HHV-6 infections. Confirmation of CNS infection with HHV-6 in some patients with CFS was obtained by the detection of HHV-6 DNA in the cerebrospinal fluid (CSF) of 20% (7/35) of the CFS patients studied.

CONCLUSION: These studies demonstrate that a sizable proportion (30% to 70%) of patients with CFS suffer from an active persistent infection with HHV-6 which may account for all or many of the clinical manifestations of their disease. Active HHV-6 infections may be especially prevalent in CFS patients with CNS involvement, consistent with the highly neuroinvasive nature of HHV-6.


Presented at the Fourth International American Association for Chronic Fatigue Syndrome Conference October 12-14, 1998
 

anciendaze

Senior Member
Messages
1,841
Likes
4,790
Can't believe that the connection to HHV-6 was already well known in 1998. If all these weirdos who block a scientific approach towards CFS, would be gone, we could be far further.
Unfortunately, if you took a vote those weirdos would predominate. The connection to HHV-6 has been perceived as discredited, like connect with EBV, because it does not always appear. We have entire generations of researchers who believe the textbook cardboard about how the etiology of well-understood diseases was uncovered, and lack experience with anything outside textbooks. We also have generations of physicians who have learned that the route to success involves 7 minute examinations and careful attention to only running tests which are billable to insurance or government. The idea that disease did not study the same textbooks, and is not required to obey human regulations is generally dismissed, partly because it is upsetting, and partly because business-as-usual produces good results for those who don't suffer from this illness.

Reactivation of latent viruses is in textbooks, as illustrated by shingles. This is well-known in connection with chicken pox, but the conditions of reactivation are generally obscure. Case histories of CFS/ME patients do seem to show an elevated rate of occurrence of shingles, but, for most in the medical profession, this is the end point of the problem. Few have been reasoning about why this should be. Reactivation of latent viruses not in textbooks generally gets ignored. There is a problem sorting through the mass of detail and connecting the dots.

All human beings have "bounded rationality". When you overload them with detail, supply conflicting evidence, and put them under pressure of time, or high-value attached to mistakes, both the speed and quality of decisions goes down. All the people who have made that effort are classified as enthusiasts with suspect motivations.
 

jewel

Senior Member
Messages
195
Likes
9
Great points, anciendaze. Science and medicine prefer the parsimonious answer; multiple infections, multiple system involvement, however true, are not parsimonious. (XMRV, if it turns out to be the puppet-master, is ...) Further, we have the CDC and their ilk "educating" physicians that CFS is caused by abuse and needs to be treated by CBT, GET, and anti-depressants. That is enough to actually make me depressed! Good day, J.
 

Bob

Senior Member
Messages
16,455
Likes
34,047
Location
England (south coast)
Can't believe that the connection to HHV-6 was already well known in 1998. If all these weirdos who block a scientific approach towards CFS, would be gone, we could be far further.
Yes, I agree, and now that Martin Lerner has had success at treating ME/CFS patients (who have a herpes virus) with anti-virals, then he should be getting proper government funding to do large scale trials... But I can't see that happening!
 

Bob

Senior Member
Messages
16,455
Likes
34,047
Location
England (south coast)
Unfortunately, if you took a vote those weirdos would predominate. The connection to HHV-6 has been perceived as discredited, like connect with EBV, because it does not always appear. We have entire generations of researchers who believe the textbook cardboard about how the etiology of well-understood diseases was uncovered, and lack experience with anything outside textbooks. We also have generations of physicians who have learned that the route to success involves 7 minute examinations and careful attention to only running tests which are billable to insurance or government. The idea that disease did not study the same textbooks, and is not required to obey human regulations is generally dismissed, partly because it is upsetting, and partly because business-as-usual produces good results for those who don't suffer from this illness.

Reactivation of latent viruses is in textbooks, as illustrated by shingles. This is well-known in connection with chicken pox, but the conditions of reactivation are generally obscure. Case histories of CFS/ME patients do seem to show an elevated rate of occurrence of shingles, but, for most in the medical profession, this is the end point of the problem. Few have been reasoning about why this should be. Reactivation of latent viruses not in textbooks generally gets ignored. There is a problem sorting through the mass of detail and connecting the dots.

All human beings have "bounded rationality". When you overload them with detail, supply conflicting evidence, and put them under pressure of time, or high-value attached to mistakes, both the speed and quality of decisions goes down. All the people who have made that effort are classified as enthusiasts with suspect motivations.
anciendaze, you have some fascinating philosophical insights into the nature of the human race...
And when you put your thoughts together with Diesel's signature quote:

A scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it.
- Max Planck
...then I think it kind of sums up the limitations of human nature with regards to scientific progress.
 

SOC

Senior Member
Messages
7,849
Likes
16,365
Great points, anciendaze. Science and medicine prefer the parsimonious answer; multiple infections, multiple system involvement, however true, are not parsimonious. (XMRV, if it turns out to be the puppet-master, is ...) Further, we have the CDC and their ilk "educating" physicians that CFS is caused by abuse and needs to be treated by CBT, GET, and anti-depressants. That is enough to actually make me depressed! Good day, J.
I've been arguing for a long time that medicine, especially that practiced by our PCPs, absurdly ignores a major player in our universe and that player is dynamics. The idea that things change, the ways they change, and the meaning of those changes is completely lost to medicine. Our bodies are full of controllers that regulate most of our processes by continuously adjusting a variety of factors. But how often do our PCPs take one data point and then think they understand what is going on? If an engineer treated a machine in the same way, s/he'd be laughed out of the industry.

Human bodies are very complex machines and while sometimes the parsimonious answer is the right one, other times those who claim to be experts on human bodies need to consider the complexities -- multiple infections, multiple system involvement, continuously changing factors and the controllers that are supposed to be regulating them.

Maybe they just can't handle the math. :Sign giggle:
 

SOC

Senior Member
Messages
7,849
Likes
16,365
I've just skimmed this thread, and might have missed something, but I think there is another way this tricky rascal of a virus can operate which causes endless confusion. Consider this a conspiracy theory which blames the virus for deliberately misleading both immune system and doctors.
[snip]
The confusion I suspect in different kinds of onset comes from two sources. One is that this, like many, many infectious diseases, produces a spectrum of illness. At one extreme, we have people infected, but completely asymptomatic. (They may outnumber people with symptoms.) At the other extreme, we have people felled quickly by "the worst flu of my life" who know the day their illness began. In between we can expect to have a continuum of responses.

The second source of confusion is that the illness which catches our attention may not be the original XMRV infection. We may start out asymptomatic, then develop symptoms when a different infection stresses the specifically weakened immune pathways activated to fight it.

My own suspicion here is that this is the connection with vaccination. I tend to doubt the vaccine itself carries the virus. There are already too many available routes of transmission to require that assumption, and the times when people are vaccinated tend to occur when exposure to those is greatest. What I'm guessing is that the immunization exposes a defect previously introduced by XMRV.

Finally, here is something which might be more original, the infection which catches our attention could easily be an earlier viral infection which was driven into latency by a healthy immune system, then reactivated when XMRV crippled defense against latent viruses.
[snip]
Some great ideas here, anciendaze! I like a virus conspiracy theory. :D

The vaccination theory works well with my daughter's experience. She came down with the same sudden onset illness I did, but recovered and remained in remission for most of the following 4 years or so. Then, following a VZV booster, she had a bad crash from which she never fully recovered. A year later she was diagnosed with persistent HHV-6.

I've suspected that if XMRV is a player, we may have been infected long before our sudden onset illness -- for her, maybe even at birth. If the XMRV was slowly degrading our immune system function, then when we both ran into a nasty virus that put a big demand on our immune systems, we had a sudden onset viral illness. That demand on our immune systems perhaps allowed HHV-6 to reactivate. My daughter's immune system was strong enough to keep it under control better than mine for 4 years, but the addition of a live herpes virus (VZV booster) was enough of an insult to her immune system, that the HHV-6 infection got out of control and she could no longer get back into remission.

By this argument, the XMRV could be a player only in that it slowly weakens the immune system. The sudden onset illness would then be only the really nasty virus that broke the camel's back, so to speak.
At that point, our immune systems were too weak and/or overloaded to keep latent infections in latency (HHV-6, in our case) and our symptoms are mostly due to our immune systems struggling to keep latent infections in check and failing.

So, by this logic, the sudden onset wasn't XMRV, XMRV wasn't transmitted in the VZV booster, and our symptoms are not caused directly by XMRV, and yet XMRV could be at the root of our health problems.

Just thinking "out loud"....