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The Potential Importance of the XMRV Retrovirus to Autism

Posted Apr 01 2011 12:00am

XMRV By Kent Heckenlively, Esq.

Although I’ve been a science teacher for the past five years I find that when I’m confronted with new information I want to explain to people I fall back on the strategies I used during the fifteen years I was a lawyer. I hope you'll consider this article in that light, as essentially an opening statement.

I think it’s important to note I don’t refer to this as a closing argument. I consider this to be the beginning of a discussion, not the end.

In a typical opening statement a lawyer reviews the evidence, the theories which will be presented, but doesn’t go into exceptional detail to prove every single point. That’s what the trial is for. And so, while each one of the points I want to make could be abundantly expanded upon, my intention is to present a brief overview of the major issues regarding the potential importance of the XMRV retrovirus to autism.

As a reader I think you'll be impressed by the number of observations which can be explained as a consequence of XMRV infection.  Similarly, disturbing questions are raised about the role of vaccines in the spread of this retrovirus.  When our understanding of how XMRV disregulates the immune system is as complete as our understanding of how various toxins can cause similar disruptions we may be able to better help those children for whom recovery remains a distant mirage.

XMRV background - XMRV (xenotropic murine leukemia virus-related virus) was discovered in 2006 by scientists working at UCSF and the Cleveland Clinic in the tumors of men with aggressive prostate cancer.  It's important to understand the difference between a typical virus and a retrovirus like XMRV.  A typical virus enters a cell, hijacks the cellular machinery to make viral particles, then causes the cell to burst, spreading viral particles throughout the body.  A retrovirus enters a cell and inserts itself into the DNA of the host, often remaining dormant for years.  I've mentioned it before, but my daughter with autism/seizures, my wife with psoriasis, and my mother-in-law with celiac sprue have all tested positive for XMRV.  I have tested negative.

In 2009 XMRV was linked with chronic fatigue syndrome/ME. An abstract presented at a meeting in 2010 from a small group of children with autism found that 82% of the children tested positive for the XMRV retrovirus.

The scientists working on this research believe XMRV is stimulated by three things, and this is where it starts to become relevant to the autism community.

 Inflammation – Any inflammation of the body tends to promote replication of XMRV. Our community has long observed how many children were seemingly normal before a vaccination and much different after one. A vaccination by its very design is supposed to create a mild inflammatory response. This mild inflammatory response may be the thing which sets off autism in the majority of children, although it must also be said that the same result could likely be achieved by a simple cold or fever.  You can read my previous post on this HERE .

Understanding the role of inflammation also sheds some light on why the gluten/casein diet works for some people, like it did very effectively for my son, Ben.  XMRV is a slowly replicating virus, so that any inflammation acts like fuel for it. We quickly got him on the gluten/casein free diet, and so we in essence starved the virus, allowing his immune system to launch a very successful attack.

Stress (cortisol hormone) – The cortisol hormone will promote replication of XMRV. I find this interesting because in its’ initial modern presentation in the 1980s chronic fatigue syndrome/ME seemed to strike mainly high-powered professional people who were often under a good deal of stress. From the standpoint of the autism community I find this intriguing because the most successful therapy program for my daughter has been the Son-Rise program which endeavors to create a loving and supportive environment around the child. It has in no way been a cure, but it has been an excellent way in which to interact with her. Many families I know have had good success with Son-Rise or other programs with similar philosophies and understanding this aspect of XMRV provides an explanation for those results.

Sex hormones (testosterone and estrogen) – The sex hormones promote replication of XMRV. Our community has long noted the 4-1 gender disparity between boys and girls stricken with this disorder, as well as the fact that when girls are affected, they tend to be the more severe cases. I also have to note that for those with seizure disorders, particularly the girls, tend to have an increase in their seizures as they enter puberty. I also have to point out that there is a group in the autism community who encourages the use of the medication, Lupron, which has the effect of blocking testosterone. Other medications which may block hormones are also on the market.

Low glutathione levels – Those with chronic fatigue syndrome/ME and autism both tend to have low glutathione levels. Low glutathione levels will increase susceptibility to viral infections, increase virulence, and impair resolution of viral infection. Our community has long reported positive effects from high levels of supplemental glutathione.

Problems with methylation - Autism researchers have long noted that there appear to be problems with methylation (cell to cell communication) in children with autism.  Numerous physicians have come up with strategies for overcoming these blocks, but the question of why there should be such problems with methylation have remained unanswered.  XMRV researchers have found that XMRV integrates preferentially at the start of CpG islands in the human genome, at locations essential for proper methylation.  This simple finding more than anything else may explain the variety of abnormalities in the immune and neurological systems of children with autism.  A recent publication on XMRV affecting gene expression can be found  HERE .

High cytokine levels – Cytokine levels are markers of inflammation in the body and the results from children with autism tend to show high levels, particularly things like TNF-alpha. A recent test from my daughter showed her TNF-alpha levels at more than 6x normal.   This is a level which might be found in an AIDS patient.  (After two months on a TNF-alpha blocker I have been able to reduce this marker by approximately 40%, although it is still high.)  Many commentators have noted how the immune profiles of many children with autism resemble those of AIDS patients, but  without the deadly outcome of HIV.

The natural killer cell anomaly - One of the hallmarks of infection by the HIV retrovirus and the subsequent development of AIDS is low numbers of natural killer cells which would normally fight off infection.  Thus, during the AIDS epidemic one of the common questions asked was the level of somebody's B or T cells.  Curiously, my daughter has slightly elevated levels of natural killer cells.  High cytokine levels and normal or elevated levels of natural killer cells make no sense.  To make an anology, it's a little like saying there's a neighborhood with a lot of cops walking the beat, but the crime rate keeps going up.  Aren't the police making arrests?  And if not, why not? 

Similar observations made by Dr. Jeff Bradstreet have recently led him to conclude that whatever is happening in our children's bodies (and he believes some sort of viral infection to be at the root of it), is effectively bliding the immune system.  Figuring out how to restore sight to the immune systems of our children might be a very effective tool in fighting this retrovirus.

Vitamin D abnormalities – One need look no further than the pale faces of our children to know something is wrong with their levels of vitamin D.  I’ve listened to many conflicting theories about how to fix these vitamin D abnormalities and I don't know which of them is correct. However, it seems there is broad agreement among many groups that something is wrong in regards to vitamin D, and possibly the vitamin D receptor.  This is from a recent article in Columbia magazine describing the work of scientists Mady Hornig and Ian Lipkin.

When they looked for metabolic differences between the Norwegian children who’ve been diagnosed with autism versus those who don’t appear autistic, they discovered that the autistic kids are three times as likely to have elevated levels of a protein found in people who are vitamin D deficient; the body produces it in a desperate attempt to squeeze as much benefit as possible from the vitamin D that it does receive . . . Hornig’s previous research provides some clues about what to look for. She’s demonstrated in laboratory studies that mice who experience viral or bacterial infections early in life go on to display autistic-like behaviors: they avoid each other and do back flips obsessively. Hornig suspects that a lack of vitamin D can exacerbate the dangerous effects of an infection, as the vitamin is known to bolster the immune system. HERE

Co-Infection by Other Pathogens – The current hypothesis is that XMRV sets up an immune deficiency in the body, thus rendering it vulnerable to infection by other pathogens such as Epstein-Barr, CMV, HHV-6 (my daughter is also positive for HHV-6, type B) and bacterial infections as well. What is not known, but strongly suspected, is that this mosaic of infections increases the severity of the disease process in the patient.

Other commonalities between patients with Chronic Fatigue Syndrome/ME and Autism – Both groups share common clinical symptoms such as immune disregulation, increased oxidative stress, heavy metal retention, and mitochondrial insufficiency. Heavy metal retention would be a consequence of a lack of energy, as well as increasing the virulence of any pathogen. Many have observed that in addition to their ability to remove metals from the body, chelators often have strong anti-viral properties.

Contamination issues – There is a political dimension to the charge of contamination, namely that those with chronic fatigue syndrome/ME have psychological problems, rather than a devastating neurological and immune disease. The original research performed by the Whittemore-Peterson Institute which linked XMRV to chronic fatigue syndrome/ME used four different forms of detection, including
1.  Serology,

2.  Western blot,

3.  Isolation of proviral DNA, and

4.  Isolation of virus in cell culture.

In addition XMRV particles have been photographed by electron microscope as they have exited from the lipid membrane of an infected cell, an impossibility for a lab contaminant.  (I have provided a picture of this at the top of my post.)

The negative studies have generally only used polymerase chain reaction (PCR) without first using techniques to increase replication of the retrovirus. The retroviral particles are fragile and continued thawing and refreezing of blood samples can destroy evidence of the retrovirus. Proper blood storage and testing procedures are critical.

One need only consider that Canada, the United Kingdom, Australia, and the United States have all approved a ban on blood donations from persons who have ever had chronic fatigue syndrome/ME to understand the severity of this threat as perceived by public health officials, even though many questions remain unanswered.  The recommendation by the FDA panel was probably the strongest in the world, adding a specific question to their intake form about chronic fatigue syndrome/ME.

There has also been strong criticisms of the selection of patients, who in the eyes of many did not even have a diagnosis of chronic fatigue syndrome/ME, but rather lesser conditions like depression. Other commentators have pointed out that the blood in test tubes cannot make anti-bodies to a lab contaminant. Only the body can make anti-bodies. Anti-bodies to XMRV have been found in patients with chronic fatigue syndrome/ME as well as my daughter with autism.

The claims of contamination may be quickly dispatched if accounts of a recent breakthrough  in genomic research are to be believed. According to these accounts  the bio-tech company, Chronix Biomedical has developed the ability to read an entire human genome within six hours.  This has given them the ability to identify those areas in which XMRV has inserted itself into the DNA of those with chronic fatigue syndrome/ME. 

These reports claim Chronix has looked for and found the predicted flanking DNA sequences on both sides of XMRV recovered from human samples and are expected to publish these findings in the next few months.  Lab contaminants do not insert themselves into DNA.  If this account is true it will be powerful scientific validation of XMRV as a significant human pathogen.  A recent review of these issues was published by the University of Hamburg and can be read  HERE .

Where did XMRV come from? – I thought I’d quote from a recent letter published in The Lancet entitled "Mouse Viruses and Human Disease." While it began by noting the claims of contamination it quickly seemed to take the opposite point of view.

Nevertheless, the paper by Lombardi and colleagues that began this debate provided solid evidence based not only on the molecular identification of the virus, but also on the immunological responses of the host (virus-specfic antibodies), viral expression in patients’ peripheral blood mononuclear cells (flow cytometry), and an infection model (infection of cultured human cells from patients’ samples). The immunological and infection evidence cannot be explained by nucleic acid contamination. Thus, the only explanation for the molecular evolution data, from a study by Hue and colleagues, is that patients have been infected by a common source of XMRV and not through human contact.

Once a virus is endogenised, it is forced to follow the evolutionary rate of the host. Since XMRV is integrated in cell-lines the virus evolution is restricted to the host’s pace of evolution, and viral descendants have none or minimum sequence diversity. Thus, if a contaminated product, previously cultured in cell-lines is administered to people then the infections would provide the evolutionary patterns reported by Hue and colleagues. If the immunological data reported by Lombardi and colleagues are correct, then we need to trace the common source for these infections to prevent possible public health concerns. Products from cell-lines should be the first candidates.  HERE

It’s difficult to escape the conclusion that what they’re talking about are vaccines which often use viruses weakened by passing them through animal tissue. What other biological products are "cultured in cell lines" and "administered to people"?

Could we be looking at a vaccine "two-fer" in which not only was this retrovirus created and spread through the process of developing a vaccine, but that once established in the human population, subsequent vaccines, even if they didn’t contain XMRV, would stimulate replication in those already infected?

Sometimes you think you understand everything about a given subject, then you get new information and think to yourself, "My God, could it be even worse than I’d imagined?" I have had many such moments in my investigation of XMRV.  You can read more from my previous article  HERE

 Closing – As I end my opening statement I hope what follows is not a trial, but a robust discussion in the autism community on whether the idea that XMRV may be linked to the problems of our children is a valid area of inquiry. I must note that the autism community has already developed tools to attack many of the problems which are linked to XMRV, from ways to lower inflammation, to normalizing glutathione levels, fighting other pathogens, and overcoming blocks to methylation.

Physicians like Dr. Jeff Bradstreet are also looking at may possibly be new tools in this fight, such as getting the vitamin D receptor to work properly, thus avoiding the need for anti-retrovirals.  These may pose risks to the health of many of our children, (particularly in their common impairment of mitochondrial functions),  which cannot be fully evaluated at this time.  If the immune system can be restored to proper functioning it may be enough to overcome any lingering XMRV or other pathogens.  The headline from a recent post by Dr. Bradstreet read, "Why I Am More Hopeful Than Ever about Autism, ME/CFS . . . TNF-Alpha, and the Viral/Pathogen Connection"  HERE   and then proceeds to discuss many of the very same issues I have covered.

After our robust discussion it's my hope that there will be renewed optimism about strategies which may help those children who have not yet enjoyed the benefits of recovery.

Kent Heckenlively is a Contributing Editor to Age of Autism

 

Posted by Age of Autism at April 08, 2011 at 5:45 AM in Current Affairs , Kent Heckenlively , Science Permalink

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