Is Chronic Fatigue Syndrome Caused By A Virus?

As with many scientific discoveries, there is an interesting back story here.

The story begins with a biologist, Robert Silverman of the Cleveland Clinic Foundation in Ohio, investigating if prostate cancer is caused by a virus.

Actually, the story begins a bit earlier than that. Scientists have known that viruses can cause cancer since the early 20th century.

In 1909 Peyton Rous discovered that a virus could cause sarcomas in chickens. For discovering the Rous Sarcoma Virus, Dr. Rous was awarded the Nobel Prize in 1966. This discovery led directly to the discovery of cellular oncogenes (genes that cause cancer) by Bishop and Varmus, which also was rewarded with a Nobel Prize.

Subsequently, numerous other human cancers have been associated with viral infections. The most important of these is Burkitt’s lymphoma. Burkitt’s lymphoma comes in three varieties: one form is endemic to sub-Saharan Africa and is most likely caused in large part by infection with a virus called Epstein-Barr Virus (EBV, which also causes mono), one form is sporadic (as opposed to endemic), and one form is associated with immunodeficiencies such as AIDS. The endemic form of Burkitt’s lymphoma typically causes a large, painful jaw mass, while the sporadic form more commonly involved the intestines. Interestingly, another name for EBV is Human Herpesvirus-4 (HHV-4). EBV, or HHV-4, also causes nasopharyngeal carcinoma in southeast Asia (and elsewhere). It is clear that there is a real connection between viruses and cancer.

Now back to Robert Silverman, who discovered a new retrovirus called XMRV.

The retrovirus was very similar to MLV, a group of viruses that can cause cancer and neurological and immunological diseases in mice. Silverman found XMRV in a subset of prostate tumours, and more recent research found a stronger correlation between XMRV and aggressive prostate tumours.

We should pause for a moment and explain the difference between a virus and a retrovirus. A virus is a very simple organism – basically a protein shell containing a little DNA. Viruses need to find hosts because they lack the tools to multiply on their own.

Cells also contain DNA, but cells (especially those of complex organisms such as humans) have ridiculous amounts of DNA. Most of the instructions in DNA used by cells on a daily basis are for creating proteins. Since mistakes are most likely to occur proportionally to how often DNA is copied, a system using RNA minimizes copying by only duplicating the specific section of DNA needed to build a specific protein. RNA is slightly different than DNA on a molecular level, so cellular machinery can respond to it but not to DNA. A cell which needs a particular protein manufactured goes through the following (simplified) steps:

1. A portion of DNA is translated into RNA.
2. RNA is sent to the endoplasmic reticulum.
3. The specified protein is built.

A standard virus hijacks the cell’s machinery by inserting DNA, which gets translated into RNA, which is then made into the specified protein; only in that case the protein is the virus.

Retroviruses are more insidious. They contain RNA rather than DNA. When a retrovirus attacks a cell, the RNA gets translated into DNA, which then gets incorporated into the cell’s own genome. Rather than hijacking the cellular machinery for their own nefarious plans, they Borg the cell. From then on, every time the cell multiplies it is bringing the virus along with it. Our genome is littered with scars from ancient battles with retroviruses which may have fundamentally shaped us into what we are today.

Alright, enough with the interruptions already.

Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nevada, asked Silverman to see if there was a connection to chronic fatigue syndrome.

Mikovits asked Silverman to analyze the blood samples of 101 CFS patients and 218 healthy controls. The authors detected XMRV DNA in the immune cells of 67% of the CFS patients but in only 3.7% of healthy controls. The authors also showed that the virus was able to spread from infected immune cells to cultured prostate cancer cells and that the virus’s DNA sequence was more than 99% similar to the sequence of the virus associated with prostate cancer. The findings were published in Science.

So far, although the results are encouraging, there has only been one pilot study completed. The magic which makes science work is verification and duplication of results.

William Reeves, principal investigator for the Centers for Disease Control and Prevention (CDC)’s CFS public health research programme, says the findings are “unexpected and surprising” and that it is “almost unheard of to find an association of this magnitude between an infectious agent and a well-defined chronic disease, much less an illness like CFS”.

But Reeves is cautious. “Until the work is independently verified, the report represents a single pilot study,” he says. According to Reeves, the CDC is already trying to replicate these findings. He also notes that CFS is a heterogeneous disease and likely arises from a combination of many factors.

The Wall Street Journal has a heartbreaking example of the suffering caused by CFS:

Ms. Whittemore-Goad says she was a regular school girl, playing sports and involved in school activities, until the age of 10, when she became ill with a monolike virus that she couldn’t shake. She said doctors first told her parents that the illness was psychological, that she had school phobia and was under stress from her parents. “We kept searching for an answer,” says Ms. Whittemore-Goad, who says lymph nodes in her groin were so painful that her brothers and sisters used to have to carry her upstairs. She was diagnosed at age 12 with chronic-fatigue syndrome.

Over the years, doctors have treated her symptoms, like intense headaches and severe pain, but the illness persists. She has had her gallbladder, spleen, and appendix removed because they became infected. She tried an experimental drug that she says gave her relief for years, but she then started experiencing side effects and had to stop taking it. Recently the illness has become worse; she began suffering seizures and can no longer drive.

Go read the whole thing.

If this virus is the cause of CFS, diagnosis and detection can be done with a simple blood test. Antiretroviral therapies designed in the fight against HIV are under investigation as a potential cure. The story is not yet over but we remain hopeful that this breakthrough represents the real deal for sufferers of CFS.

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