2009-10-22

New Cause of Chronic Fatigue Syndrome Perhaps Found

New Cause of Chronic Fatigue 
Syndrome Perhaps Found

Scientists near the epicenter of one of the largest known outbreaks or epidemics of chronic fatigue syndrome (CFS) have published an astounding finding:  about two-thirds of people with CFS have traces of a novel virus, XMRV.  Only about 3% of those without CFS have traces of XMRV in their tissue.  The investigators suspect about 100% of people with CFS actually have this virus in them.

If the findings hold up, chronic fatigue syndrome will suddenly cease to be a problem of the mind, but will be known as an infection, a retroviral infection.  The only proven retroviral infection in humans is HIV.  But it seems very likely that reflects our ignorance and that retroviruses play a much larger role in human life than we know.

What follows is my current understanding of retroviruses, a group of germs it looks like we better learn much more about.

The Basics About Viruses
Viruses are a very ancient and peculiar part of all life.  In essence, they are just traveling bits of information.  The information is contained in their tiny bits of DNA or RNA whose only purpose is to make more viral DNA or RNA.

A typical virus is just a strand of a few genes of DNA packaged in a protein that contains the right combination to enter its target cell.  The viral DNA finds its way into the cell's DNA and takes over.  Soon the poor infected cell stops what it was supposed to do and starts making an astounding number of copies of viral DNA and its coating proteins.  The cell explodes, releasing vast numbers of new viruses to repeat the cycle.  This is how nearly all the usual viral infections we experience, like colds, flus, measles, mumps, chickenpox work.

The nice part of the usual DNA virus is that a dead cell cannot dysfunction, so the body can replace it, you heal, all is well.

Some Basics About Retroviruses
The retroviruses are far more insidious.  They have RNA in their centers. The RNA enters the cell and directs the cell to make DNA that inserts itself very gently into the cell's DNA.  Usually this does not kill the cell.  It continues to go about its business, but additionally starts making viral RNA, and the retrovirus reproduces.   The viral reproduction, however, does not kill the cell, and the viral DNA remains in the cell's DNA.  If you are lucky, the cell really is not harmed or changed, and life goes on unharmed or changed.

But, often, the retrovirus leaves the cell a bit altered in its usual function.  That bit of alteration often leads to serious dysfunction of critical cellular systems, such as growing.  As a result, many known retroviral infections in animals cause cancers to sprout.

If important immune system cells are infected and their function messed up, the immune system function can be jammed.  This is the problem seen in the most famous retrovirus of them all, HIV.  Infected cells include very important immune system cells, devastating normal immune function.

If XMRV is the cause of chronic fatigue syndrome, then we will have an example of the retroviral process interfering with neurological function.  

Clearly, the retroviruses can cause havoc in important functions of the body, including how cells grow, how the immune system works, and perhaps how the brain functions.

Retroviruses in Evolution
But the impact of retroviruses is clearly not limited to just causing disease.

Remember that retroviruses leave their traces in the cell's DNA?  That leads to one of their most striking properties.  Over the course of the last 3 or so billion years, retroviruses have left their DNA traces on essentially all living cells.  It turns out viruses have been around nearly as long as life.  Back when life on Earth was only single-celled organisms, essentially bacteria, viruses were already infecting cells.  Retroviruses were there all along as well, and their viral DNA has been passed along the generations of life.

As a result our human DNA is estimated to be about 10-15% ancient retroviral DNA.  When scientists sequenced the human genome, they found that vast stretches of human DNA did not encode for any known product, most of the human genome is not genes!  Not all, but about 15% of those stretches are from retroviral infections that took place over somewhere around 200 million years ago.  It is not known if these ancient retroviral sequences in our DNA do anything, but one striking possibility is that they are responsible for the development of placentas in mammals.  Soon after the egg is fertilized, the sequences of DNA that lead to the placenta forming and invading the mother's uterus appear to be retroviral in origin.

A Summary of Properties of Retroviruses
And so retroviruses are indeed a highly unusual set of infecting agents.  Their properties that we understand so far, are striking:
  • They have to create and then insert viral DNA into the cell's DNA without killing it.
  • This leads to persistence of their DNA sequences if the changes enter into reproducing cells.
  • Retroviral infections tend to be permanent changes in our DNA.
  • They do not kill cells, only change their function enough to reproduce.
  • The changes in function lead to a wide variety of sometimes very interesting, sometimes very upsetting changes in the organism's functions.  So far we know that retroviruses can:
    • Create placentas
    • Cause cancer (many, many examples in animals, perhaps prostate in humans)
    • Cause failure of the immune system
    • Cause alterations in neurologic function, e.g., chronic fatigue syndrome
The Seven Families of Retroviruses
As you might guess, we know very, very little about retroviruses.  So far about 7 families of retrovirus have been identified in humans and animals.
In the sixth family resides the most famous retrovirus, AIDS.
The proposed viral cause of chronic fatigue syndrome is in the third grouping, hence the reference to gamma retroviruses.
The fourth or delta retrovirus family contains the only other known human retrovirus, HTLV, which is closely related to HIV, but not identical.
For alpha, beta, and epsilon retroviruses, the only known examples are animal viruses that cause a variety of cell growth problems, or cancers.

Treating Retroviral Infection
The only treatment known for any retroviral infection is to stop the retrovirus from converting its own RNA into our DNA.  And that approach has only been shown to work on AIDS.

But, if HIV retroviruses can be stopped in their tracks, their is much hope others can as well.


BOTTOM LINE:


It is not yet proven that XMRV causes chronic fatigue syndrome.  The initial evidence is compelling, but compelling evidence has proven not to be proof in other situations.


Most upsetting, we cannot offer new, novel therapies for chronic fatigue syndrome just yet.  We first have to find out if XMRV is an actual cause, and then find out how to stop or reverse its effect. 


But, the discovery that a gamma retrovirus, XMRV (Xeno Murine Retro Virus, i.e., unusual rat retrovirus) may cause chronic fatigue syndrome opens a new door of understanding, and for the first time, hope for prevention and cure for this serious malady.

I suspect, that as we learn more about retroviruses, we will find that there are alot more of them in humans than we thought, and that their impact may include not just dread diseases, but some fairly vital side impacts (like forming placentas) as well.


I will keep this web site updated as we learn more about the cause of chronic fatigue syndrome, and retroviruses.

Dr. Lavin

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