WPI Finds High Levels of Retrovirus in ME/CFS Patients

Cort

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HOTPOINTS

Prevalence - XMRV virus found in approximately 2/3 of ME/CFS patients in locations across the US. Dr. Mikovits sites unpublished evidence suggesting that that percentage could be much higher.

Two Diseases - XMRV is found in high levels in two diseases; aggressive forms of prostate cancer and ME/CFS. Both have defects in the RNase L enzyme that controls the interferon immune response.

CONSORTIUM OF RESEARCHERS DISCOVER RETROVIRAL LINK TO CHRONIC FATIGUE SYNDROME
Scientists have discovered a potential retroviral link to chronic fatigue syndrome, known as CFS, a debilitating disease that affects millions of people in the United States. Researchers from the Whittemore Peterson Institute (WPI), located at the University of Nevada, Reno, the National Cancer Institute (NCI), part of the National Institutes of Health, and the Cleveland Clinic, report this finding online Oct. 8, 2009, issue of Science.

"We now have evidence that a retrovirus named XMRV is frequently present in the blood of patients with CFS. This discovery could be a major step in the discovery of vital treatment options for millions of patients," said Judy Mikovits, Ph.D., director of research for WPI and leader of the team that discovered this association. Researchers cautioned however, that this finding shows there is an association between XMRV and CFS but does not prove that XMRV causes CFS.

The scientists provide a new hypothesis for a retrovirus link with CFS. The virus, XMRV, was first identified by Robert H. Silverman, Ph.D., professor in the Department of Cancer Biology at the Cleveland Clinic Lerner Research Institute, in men who had a specific immune system defect that reduced their ability to fight viral infections.

"The discovery of XMRV in two major diseases, prostate cancer and now chronic fatigue syndrome, is very exciting. If cause-and-effect is established, there would be a new opportunity for prevention and treatment of these diseases," said Silverman, a co-author on the CFS paper.

Commonality of an immune system defect in patients with CFS and prostate cancer led researchers to look for the virus in their blood samples. In this study, WPI scientists identified XMRV in the blood of 68 of 101 (67 percent) CFS patients. In contrast, they found that eight of 218 healthy people (3.7 percent) contained XMRV DNA. The research team not only found that blood cells contained XMRV but also expressed XMRV proteins at high levels and produced infectious viral particles. A clinically validated test to detect XMRV antibodies in patients' plasma is currently under development.

These results were also supported by the observation of retrovirus particles in patient samples when examined using transmission electron microscopy. The data demonstrate the first direct isolation of infectious XMRV from humans.


"These compelling data allow the development of a hypothesis concerning a cause of this complex and misunderstood disease, since retroviruses are a known cause of neurodegenerative diseases and cancer in man," said Francis Ruscetti, Ph.D., Laboratory of Experimental Immunology, NCI.

Retroviruses like XMRV have also been shown to activate a number of other latent viruses. This could explain why so many different viruses, such as Epstein-Barr virus, which was causally linked to Burkitt's and other lymphomas in the 1970s, have been associated with CFS. It is important to note that retroviruses, like XMRV, are not airborne.

"The scientific evidence that a retrovirus is implicated in CFS opens a new world of possibilities for so many people," said Annette Whittemore, founder and president of WPI and mother of a CFS patient. "Scientists can now begin the important work of translating this discovery into medical care for individuals with XMRV related diseases."

Dan Peterson, M.D., medical director of WPI added, "Patients with CFS deal with a myriad of health issues as their quality of life declines. I'm excited about the possibility of providing patients, who are positive for XMRV, a definitive diagnosis, and hopefully very soon, a range of effective treatments options."

The Whittemore Peterson Institute for Neuro Immune Disease exists to bring discovery, knowledge, and effective treatments to patients with illnesses that are caused by acquired dysregulation of both the immune system and the nervous system, often resulting in lifelong disease and disability. www.wpinstitute.org.

The Lerner Research Institute is home to Cleveland Clinic's laboratory, translational and clinical research. Its mission: to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. More than 1,200 people in 11 departments work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious disease. The Institute also is an integral part of the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.


The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <www.nih.gov>.
-------------------------------
REFERENCE: Lombardi VC, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, and Mikovits JA. Detection of Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome. Online October 8, 2009. Science.
 

Cort

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WPI Question and Answer on XMRV

Q and A from the WPI website http://wpinstitute.org/xmrv/xmrv_qa.html

What is XMRV?

Researchers at the Whittemore Peterson Institute in collaboration with the National Cancer Institute and the Cleveland Clinic, have recently discovered the presence of a retrovirus in blood samples from patients diagnosed with chronic ME/ CFS. The human retrovirus, identified as XMRV, has now been found to be in over 95 percent of the patients’ blood samples in this study group.

XMRV is a human retrovirus and is similar to HIV and HTLV-1. It was first identified by Dr. Robert Silverman, in prostate cancer tissue of men with a specific genetic defect in their antiviral defense pathway. Prior to the Whittemore Peterson Institute study, XMRV had not been isolated from a human diseased population or been shown to be infectious and transmissible.

What is the link between XMRV and ME/CFS, fibromyalgia and other neuro-immune diseases?

Our initial research showed that 67% of the ME/CFS patient samples tested positive for XMRV. Further work has found that 95% tested positive. Work continues to understand how this virus works within neuro-immune diseases, but this discovery proves a significant correlation between this serious retrovirus and these diseases.

A few fibromyalgia samples were tested and yes, they were positive. However the sampling was very small, and testing will have to continue on a much larger scale to begin to draw significant conclusions. In addition, many patients with ME/CFS have been given the diagnosis of fibromyalgia when in fact they have ME/CFS and fibromyalgia.

How is XMRV transmitted?

XMRV is thought to be transmitted through body fluids such as blood, semen, and mother’s breast milk but is not transmitted through the air. It is not known whether XMRV is more easily transmitted than other human retroviruses.

What does it mean if I am infected with XMRV?


In other studies XMRV has been detected in very aggressive cancerous prostate tumors. We do not know all of the health ramifications of XMRV or ME/CFS, but we do know that some people with ME/CFS, have on average a lower life expectancy than someone without this chronic disease. One may have XMRV and not have ME/CFS as evidenced by positive results of 3.7 percent of our control samples.

Why was XMRV looked for in neuro-immune diseases?


Patients who have been diagnosed with ME/CFS have been shown to have a unique immune deficiency in a part of their antiviral system called the RNase L pathway. This pathway was also deficient in men whose cancer samples were first used in the discovery of XMRV. In this study, however, Whittemore Peterson Institute researchers have found XMRV in patients without an RNase L pathway deficiency. It is not known if XMRV causes this deficiency or if patients with this deficiency are more susceptible to the virus’ effects or both.

Where did the Whittemore Peterson Institute get the blood samples used for this study?


The blood samples used in this historic study were collected from several different regions within the United States and included both a known ME/CFS population and a control group. Of those diagnosed with ME/CFS, over 95 percent have recently been found to have antibodies to XMRV in their blood.

Can you catch ME/CFS?

Causation of ME/CFS is likely to be a multi-factorial process which occurs in a susceptible person with common viral co-infections. Chronic fatigue syndrome (ME/CFS) is a complex, systemic neuro-immune disease that is estimated to affect over one million Americans and 17 million people worldwide. ME/CFS has traditionally been diagnosed by the exclusion of other similarly presenting conditions, such as MS and lupus, and by a series of symptoms; making the diagnosis an expensive and difficult process. Until now, a single viral link (while suspected by many) had not been made because so many common viruses have been found to be reactivated in persons with ME/CFS. This finding suggests a role for XMRV in the pathogenesis of ME/CFS and creates a better understanding of the disease. Our work suggests but does not prove that XMRV may be the underlying cause of ME/CFS. Much additional work needs to be done to understand how XMRV causes disease and what types of diseases it is linked to it.

If I am pregnant or thinking about getting pregnant and have ME/CFS, should I be concerned about protecting my unborn child?

As a ME/CFS patient who is either pregnant or thinking about getting pregnant, you should speak with your physician regarding XMRV and safety measures you can use to minimize transmission of this virus to your child.

What can my doctor do for me if I test positive to the XMRV virus?

Research is still ongoing to determine the best treatments for those who are positive for XMRV. It is possible that antiviral therapies developed for other retroviruses may be useful against another RNA virus like XMRV. However, these are generally toxic therapies with considerable side effects making it imperative that one be very careful before beginning any new therapies. Obviously, only begin any therapies approved by your physician.

Who discovered XMRV?

XMRV was originally discovered in prostate cancer tumors by Dr. Robert Silverman. Scientists from the Whittemore Peterson Institute, Cleveland Clinic and the National Cancer Institute were the first to discover XMRV in the blood of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients.

How many retroviruses are there?


Currently there are only three known infectious human retroviruses; HIV, HTLV-1 and 2 and now XMRV. HIV causes AIDS and HTLV-1 and 2 causes T-cell leukemia and T-cell lymphoma. XMRV is the most recent retrovirus discovered to infect humans and has been linked to neurological disease and prostate cancer.

I have been diagnosed with ME/CFS and recently tested positive for XMRV. My friends and family ask that if I am sick and have a retrovirus, why do I look normal?

Like other retroviruses known to infect humans, these illnesses appear to be invisible to the untrained eye. A physician, however, can see the signs of illness, and still must carefully examine the patient to know for certain who is ill and with what disease. Many diseases fall into this category. Unless one develops a disease that creates physical lesions that people can see e.g. psoriasis, the mask of lupus or the crippling bone changes of arthritis, most people can not see how debilitating the illness actually is. In addition, each person responds differently to treatment and therefore can maintain a higher quality of health and appearance of health. In the case of HIV, many people are infected but do not appear to be ill.

Most thought ME/CFS was a woman’s disease. But XMRV has been found in men with prostate cancer and now people with ME/CFS. What does this say about ME/CFS?

ME/CFS is not a woman’s disease. In fact the epidemiological study done by Dr. Lenny Jason has shown that this disease occurs in men and women and is also prevalent in children. Instances of outbreaks in which entire families and groups of friends became ill near the same time, have been reported across the US, the UK and other countries.

Does this latest information prove once and for all that ME/CFS is not a psychological or psychosomatic illness as described by those who don’t understand the disease?

Absolutely! Actually, there are thousands of research articles showing the very real biological problems that ME/CFS patient’s experience such as low NK cell count and function, MRI and SPEC scan changes, and repeated chronic infections, to mention just a few. Only the most stubborn and misinformed individuals refuse to believe that this disease is real and serious. The process of placing poorly understood illnesses into a psychological category is very similar to what happened in the early days of MS and epilepsy before the advent of technologies which proved the illnesses were “real.” Unfortunately, many in the scientific and medical fields have not learned from their past mistakes.

Is XMRV only in the United States or is it elsewhere?


For the purposes of this study, samples were collected from many different areas within the United States. However, as with other retroviruses, there is no reason to believe that the virus is not present in all other parts of the world.
 

richvank

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Possible link to low Red blood cell oxygen levels - a protein associated with the virus can coat red blood cells possibly leading to low red blood cell oxygen levels

Dr. Reeves - 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". The CDC is however trying to replicate these findings.

Prevalence - "It's highly preliminary, but if it's in fact representative, then there are 10 million Americans with this infection, which is very similar to MLV and is now linked to two important diseases," - this is going to get a lot of study. The NIH has already convened a conference about how to go about determining how prevalent this virus is and how much illness it causes.

NATURE NEWS Virus linked to chronic fatigue syndrome

Prostate cancer pathogen may be behind the disease once dubbed 'yuppie flu'.

Lizzie Buchen

A study on chronic fatigue syndrome (CFS) has linked the mysterious and controversial disease to a recently discovered retrovirus. Just last month researchers found the same virus to be associated with aggressive prostate tumours.

CFS is marked by debilitating exhaustion and often an array of other symptoms, including memory and concentration problems and painful muscles and joints. The underlying cause of the disease is unknown; it is diagnosed only when other physical and psychiatric diseases have been excluded. Though the disease's nebulous nature originally drew scepticism from both doctors and the general public, most of the medical community now perceives it as a serious — if poorly defined — disease.

Now Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nevada, and her colleagues think they have discovered a potential pathogenic link to CFS. In patients with the disease from different parts of the United States, 67% were infected with a retrovirus known as XMRV. Less than 4% of controls carried the virus.

"I can't wait to be able to tell my patients," says Mikovits, who is also the vice president of drug development for Genyous Biomed in Henderson, Nevada. "It's going to knock their socks off. They've had such a stigma. People have just assumed they were just complainers who didn't handle stress well."

Prostate puzzle

CFS researchers have long had their eyes on retroviruses. A number of the symptoms, including fatigue and cognitive dysfunction, can occur when the immune system is dealing with a viral infection, and the disease is often preceded by a flu-like illness. Although a number of retroviruses have been hypothesized to play a role in CFS, none has ever been confirmed.

About three years ago Robert Silverman, a biologist at the Cleveland Clinic Foundation in Ohio and a coauthor of the new study, discovered a previously unknown retrovirus, XMRV, while searching for a pathogen that might contribute to prostate cancer. 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 tumours1,2.

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 Science3.

"It's scary," says Mikovits. "But it's cool. Hopefully this will finally make people change their attitudes to this disease."


Mikovits believes the association may be even stronger than the present work indicates. DNA sequencing only picks up active infections, she says, so she wants to study CFS exposure to the virus more broadly. In an unpublished investigation, she and her colleagues analyzed blood cells in about 330 CFS patients and found that more than 95% expressed antibodies to XMRV, whereas about 4% of healthy controls did.

Controversial connection

Although Mikovits acknowledges that it's premature to suggest a causal link between XMRV and CFS, she thinks it makes sense. Chronic XMRV infection in immune cells could cause them to churn out inflammatory cytokines, which are observed in some CFS patients, she says. Mikovits also points out that the MLV coat protein can disrupt red blood cells in mice, leading to low blood oxygen levels.

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.

XMRV presents its own puzzle. John Coffin, a virologist at Tufts University in Boston who has studied MLV, points out that the virus's prevalence in healthy controls "is, in some ways, an equally striking result".

"It's highly preliminary, but if it's in fact representative, then there are 10 million Americans with this infection, which is very similar to MLV and is now linked to two important diseases," says Coffin. "There's a lot we don't know, including whether XMRV causes disease, but that's always the case when the first paper, like this one, comes out."

• References

1. Schlaberg, R. et al. Proc. Natl Acad. Sci. USA 106, 16351– 16356 (2009).
2. Urisman, A. et al. PLoS Pathogens 2, e25 (2006).
3. Lombardi, V. C. et al. Science doi:10.1126/science.117052 (2009).
 

richvank

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THis sent a chill up my spine: "NCI is responding like it did in the early days of HIV,[/B]" says Stuart Le Grice, head of the Center of Excellence in HIV/AIDS and cancer virology at NCI and one of the organizers of the July workshop.
[/I]

WALL STREET JOURNAL
OCTOBER 8, 2009, 3:12 P.M. ET
Retrovirus Linked to Chronic-Fatigue Syndrome By AMY DOCKSER MARCUS

Researchers have linked an infectious virus known to cause cancer in animals to chronic-fatigue syndrome, a major discovery for sufferers of the condition and one that concerned scientists for its potential public-health implications.

An estimated 17 million people world-wide suffer from chronic-fatigue syndrome, a devastating condition about which there is little medical consensus. CFS is characterized by debilitating fatigue and chronic pain, among other symptoms, but diagnosis is generally made by ruling out other diseases, and there are no specific treatments.

Many patients say they are told by doctors that their problems are psychological, so a study showing a strong association between a virus and CFS is likely to change the field.

But the significance of the finding, published Thursday in Science, extends far beyond the community of people living with CFS. Researchers are just as concerned about the finding that nearly 4% of healthy people used as controls in the study were also infected with the virus, called XMRV. If larger studies confirm these numbers, it could mean that as many as 10 million people in the U.S. and hundreds of millions of people around the world are infected with a virus that is already strongly associated with at least two diseases.

The study was done by researchers at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nev., the National Cancer Institute and the Cleveland Clinic.

In September, researchers at the University of Utah and Columbia University Medical Center found XMRV in 27% of the prostate-cancer samples they examined. That study also showed that 6% of the benign prostate samples had XMRV. The chronic-fatigue study is the first to find live XMRV virus in humans.

Neither study conclusively shows that XMRV causes chronic-fatigue syndrome or prostate cancer. But the National Cancer Institute was sufficiently concerned to convene a closed-door workshop in July to discuss the public-health implications of XMRV infection. "NCI is responding like it did in the early days of HIV," says Stuart Le Grice, head of the Center of Excellence in HIV/AIDS and cancer virology at NCI and one of the organizers of the July workshop.

Like HIV, XMRV is a retrovirus, meaning once someone is infected, the virus permanently remains in the body; either a person's immune system keeps it under control or drugs are needed to treat it. The virus creates an underlying immune deficiency, which might make people vulnerable to a range of diseases, said Judy Mikovits of the Whittemore Peterson Institute and one of the lead authors on the paper.

So far, XMRV, known fully as xenotropic murine leukemia virus-related virus, doesn't appear to replicate as quickly as HIV does. Scientists also don't know how XMRV is transmitted, but the infection was found in patients' blood samples, raising the possibility that it could be transmitted through blood or bodily fluids.

Dr. Le Grice of the NCI said the highest priority now was to quickly develop a validated blood test or other assay that could be used in doctors' offices to determine who has XMRV. At the workshop, participants also raised the issue of protecting the nation's blood supply. Dr. Le Grice said there isn't enough evidence yet to suggest that people with XMRV shouldn't be blood donors but that determining how XMRV is transmitted was a critical issue. "A large effort is under way to answer all these questions," he said. "I do not want this to be cause for panic."

Although Thursday's scientific paper doesn't demonstrate conclusively that XMRV is a cause of CFS, additional unpublished data make it a very strong possibility. Dr. Mikovits said that using additional tests, the scientists determined that more than 95% of the patients in the study are either infected with live virus or are making antibodies that show their immune systems mounted an attack against XMRV and now had the virus under control. "Just like you cannot have AIDS without HIV, I believe you won't be able to find a case of chronic-fatigue syndrome without XMRV," Dr. Mikovits said.

At the July workshop, Dr. Mikovits also presented preliminary data showing that 20 patients of the 101 in the study have lymphoma, a rare form of cancer. The link between XMRV and lymphoma is still being investigated, but it raised the possibility that XMRV may be associated with other cancers in addition to prostate cancer. NCI's Dr. Le Grice said studies will be launched to determine whether XMRV is associated with other diseases. At the Whittemore Peterson Institute, Dr. Mikovits said they also found XMRV in people with autism, atypical multiple sclerosis and fibromyalgia.

The Science study was based on blood samples from a national repository at the Whittemore Peterson Institute collected from doctors in cities where outbreaks of chronic-fatigue syndrome occurred during the 1980s and '90s. One of the key questions that the NCI's Dr. Le Grice says must now be answered is whether XMRV shows up in large numbers of CFS patients all over the country.

Robert Silverman, a professor at the Cleveland Clinic Lerner Research Institute who is one of the co-authors of the study and one of the discoverers of the XMRV virus, said he believes the virus began in mice and then spread to humans, and that "in most cases, people's immune systems are probably able to control the virus." Researchers are already starting to test antiretroviral therapies developed for AIDS to see if they are effective against XMRV.

The work on XMRV in chronic-fatigue patients initially was funded by Annette and Harvey Whittemore and the University of Nevada, Reno. The Whittemores set up the institute in 2006 after watching their daughter Andrea suffer from chronic-fatigue syndrome for most of her life. They spent millions of their own money to pay for administrative services, office space, lab equipment and research operations. They were frustrated by the lack of government funding for scientific research into the disease.

At their home in Reno, the Whittemores' daughter, Andrea Whittemore-Goad, 31 years old, used oxygen before speaking about the devastating toll CFS has taken on her.

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.

Sitting on the couch next to her husband, whom she married six months ago after meeting, Ms. Whittemore-Goad says the news that she is infected with XMRV "made everything that has happened to me make sense." Brian Goad, her husband, said he felt relieved knowing "now we can find a way to treat and hopefully cure it." For both of them, the discovery of the virus is life-changing. There are more than 10 families in the group where family members also tested positive for XMRV. Members of the Whittemore family are now being tested.

Write to Amy Dockser Marcus at amy.marcus@wsj.com
 
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Mice

I wonder if ticks could be tested for this retrovirus. Simply because a murine retrovirus jumping species sounds a little odd to me. However ticks feed on field mice as often as deer and other mammals like *humans*. And it's blood borne. Therefore conceivably the virus could adapt i.e. jump. (Not that viruses can't jump otherwise but it isn't all that common). I think someone should encourage Eva Sapi PhD to test for this (I guess I will :D).

I do know that science works with murine retroviruses. For instance it has been used in gene therapy--a modified murine leukemia virus. Perhaps it has been used in other fields that I don't know about.
 

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Contagious:Given that infectious virus is present in plasma and blood cells, blood-borne transmission is a possibility,” write Coffin and Stoye.

RNase L - RNase L dysfunction is an old finding in ME/CFS. ]. It was recently found to be a problem in prostate cancer as well. - Both conditions are associated with dysfunction of [the antiviral enzyme] RnaseL, which is an important element of intracellular anti-viral immunity,”

Genetic Match to the Virus Associated with Prostrate cancer -

http://www.eht-forum.org/news.html?fileId=news091008073802&from=home&id=0

Emerging retrovirus turns up in new patients
Novel virus can spread between people, may lie behind other common illnesses


Electron micrograph of xenotropic murine leukemia virus-related virus (XMRV) in the blood of a chronic fatigue syndrome patient.

Source: Whittemore Peterson Institute

A retrovirus first seen in prostate cancer patients three years ago has now been discovered in the blood of people suffering from chronic fatigue syndrome (CFS), Vincent Lombardi and colleagues report1 today in Science. The virus can be passed on from person to person and may be linked with other health conditions, experts say.

“We have discovered a highly significant association between the XMRV [xenotropic murine leukemia virus-related virus] retrovirus and CFS,” write Lombardi, from the Whittemore Peterson Institute in Nevada, USA, and colleagues. Two-thirds of 101 patients included in the study had the viral DNA in their blood, compared with just 3.7% of healthy controls.

The virus could play a part in causing CFS, suggest the authors. Like HIV and other retroviruses, it could be responsible for immune and neurological effects seen in infected people. They noted signs of an immune response specific to XMRV, as well as immune and neurological symptoms in the patients they studied.

But the finding raises more questions than it answers, they caution. The virus may well have nothing to do with causing CFS.

Writing2 in an associated article, John Coffin and Jonathan Stoye call for more research to pin down the role of this virus in CFS and other diseases. “Closely related viruses cause a variety of major diseases, including cancer, in many other mammals,” they write. “Further study may reveal that XMRV is a cause of more than one well-known ‘old’ disease, with potentially important implications for diagnosis, prevention, and therapy.

The study comes on the heels of recent research suggesting a link between prostate cancer and XMRV. The viruses found in the two sets of patients are effectively identical genetically, according to Lombardi and colleagues.

Both conditions are associated with dysfunction of [the antiviral enzyme] RnaseL, which is an important element of intracellular anti-viral immunity,” explains Yasuhiro Takeuchi, from the Division of Infection and Immunity at University College London in the UK. “This could help XMRV infection in these patients.”

Cell-culture experiments conducted by Lombardi and colleagues suggest that XMRV can spread between people through transmission of either infected cells or viral particles alone. “Given that infectious virus is present in plasma and blood cells, blood-borne transmission is a possibility,” write Coffin and Stoye.

The authors note that some 3.7% of healthy controls tested positive for the virus. In the earlier study of prostate cancer patients, this figure was 5% in the control group. Putting these together, Coffin and Stoye suggest that “perhaps 10 million people in the United States and hundreds of millions worldwide are infected with a virus whose pathogenic potential for humans is still unknown.”

The form of XMRV now seen in humans can be traced back to a mouse virus, the xenotropic murine leukemia virus (MLV), explain Coffin and Stoye. This is called an “endogenous” virus because it infects reproductive cells and can therefore be passed on to offspring of infected parents. Their similarity leaves “little doubt” that XMRV emerged by cross-species transmission, they say, and this probably happened outside the laboratory.

Both MLV and XMRV belong to the group of gammaretroviruses, notes Takeuchi, which are known to cause cancer, immunological and neurological diseases in animals.

The experts are mystified as to why the virus is coming to light now. Stoye suggests one explanation could be the use of improved methods to identify novel viruses in tissues taken from different sources. “[This] reflects a continuing trend over the past 40 years for identifying novel viruses more and more quickly,” he notes.

“I expect our knowledge of XMRV in human health will expand very fast,” says Takeuchi. “I think many researchers are starting or have started to look [for it]”.
 

MEKoan

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Reeves in Nature

"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"."

It's not only really real, it's really most sincerely real!

Who knew!?

We did!

:cool:
 

Cort

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Reuters

REUTERS

Study isolates virus in chronic fatigue sufferers

Thu Oct 8, 2009 2:00pm EDT

* Virus found in 67 percent of chronic fatigue patients

* Findings show link to CSF, not proof of causation

* Discovery a major step toward treatment options

By David Morgan

WASHINGTON, Oct 8 (Reuters) - A virus linked to prostate cancer also appears to play a role in chronic fatigue syndrome, according to research that could lead to the first drug treatments for a mysterious disorder that affects 17 million people worldwide.

Researchers found the virus, known as XMRV, in the blood of 68 out of 101 chronic fatigue syndrome patients. The same virus showed up in only 8 of 218 healthy people, they reported on Thursday in the journal Science.

Judy Mikovits of the Whittemore Peterson Institute in Nevada and colleagues at the National Cancer Institute and the Cleveland Clinic emphasized that the finding only shows a link between the virus and chronic fatigue syndrome, or CFS, and does not prove that the pathogen causes the disorder.

Much more study would be necessary to show a direct link, but Mikovits said the study offers hope that CFS sufferers might gain relief from a cocktail of drugs designed to fight AIDS, cancer and inflammation.

"You can imagine a number of combination therapies that could be quite effective and could at least be used in clinical trials right away," Mikovits said in a telephone interview.

She said AIDS drugs such as non-nucleoside reverse transcriptase inhibitors and integrase inhibitors as well as nonsteroidal anti-inflammatory drugs and cancer-fighting proteasome inhibitors could be tested as potential treatments for CFS.

Takeda Pharmaceutical Co Ltd (4502.T: Quote, Profile, Research, Stock Buzz) makes a cancer drug called Velcade that is a proteasome inhibitor, although there are no reports that it has been tested against XMRV.

INCAPACITATING FATIGUE

CFS impairs the immune system and causes incapacitating fatigue, according to the U.S. Centers for Disease Control and Prevention. Sufferers can also experience memory loss, problems with concentration, joint and muscle pain, headaches, tender lymph nodes and sore throats.

Symptoms last at least six months and can be as disabling as multiple sclerosis or rheumatoid arthritis, the CDC said.

But Mikovits said there is currently no treatment for CFS aside from cognitive behavioral therapy to help patients cope with the disorder's crippling effects.

The XMRV virus is a retrovirus, like the HIV virus that causes AIDS. As with all viruses, a retrovirus copies its genetic code into the DNA of its host but uses RNA -- a working form of DNA -- instead of using DNA to do so.

Known formally as xenotropic murine leukemia virus-related virus, XMRV has also been found in some prostate tumors and is also known to cause leukemia and tumors in animals. [ID:nN07209255]

Mikovits' team said further research must now determine whether XMRV directly causes CFS, is just a passenger virus in the suppressed immune systems of sufferers or a pathogen that acts in concert with other viruses that have been implicated in the disorder by previous research.

"Conceivably these viruses could be co-factors in pathogenesis, as is the case for HIV-mediated disease, where co-infecting pathogens play an important role," the report said.

Because 3.7 percent of the healthy test population tested positive for XMRV, the researchers said several million otherwise healthy people in the United States could be infected with it. (Editing by Maggie Fox and Vicki Allen)
 

MEKoan

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"INCAPACITATING FATIGUE

CFS impairs the immune system and causes incapacitating fatigue, according to the U.S. Centers for Disease Control and Prevention. Sufferers can also experience memory loss, problems with concentration, joint and muscle pain, headaches, tender lymph nodes and sore throats."


Pinch me, I'm dreaming!

:p
 

Cort

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HOTPOINTS

Why it persists while other viruses don't. Most people apparently did get over infections but retroviral infections are a different story - "Retroviruses in general give rise to infections that persist indefinitely," says Coffin. Most other viruses are eliminated from the body.

Confident Researchers! - The whole enchilada! - In people, XMRV could explain "the entire spectrum of symptoms that have come to be known as chronic fatigue syndrome," - Dr. Judy Mikovits

The Face of Chronic Fatigue Syndrome - Annette Whittemore, one of the founders of the Whittemore Peterson Institute. "We've always known there was something out there. Now we see its face," she says.

WPI Testing Treatments - WPI will start testing the efficacy of retroviral drugs in ME/CFS soon

NPR - Virus Linked To Chronic Fatigue Syndrome by Jon Hamilton October 8, 2009

Scientists have uncovered a strong link between an unusual virus and chronic fatigue syndrome, which affects more than 1 million people in the United States.

Researchers found that two-thirds of people with chronic fatigue are infected with a retrovirus called XMRV, according to a new study in the journal Science Express. XMRV has also been found in the tumors of some prostate cancer patients.

Scientists say it's too soon to say whether XMRV actually causes chronic fatigue.

People with the syndrome feel tired even after a good night's sleep. Many also have debilitating pain in their muscles or joints, trouble concentrating and immune problems.

The new study compared blood samples from 101 chronic fatigue patients with samples from 218 healthy people. About 67 percent of the sick people had XMRV, compared with fewer than 4 percent of healthy people.

Understanding The Retrovirus

XMRV and other retroviruses are known to infect immune cells. XMRV has been found in some prostate tumors. It's also related to a retrovirus that causes cancer in animals.

The best-known retrovirus is HIV. But scientists say XMRV is simpler, and not a close relative.

In people, XMRV could explain "the entire spectrum of symptoms that have come to be known as chronic fatigue syndrome," says Judy Mikovits, one of the study's authors and research director of the Whittemore Peterson Institute at the University of Nevada, Reno.

But scientists have pointed to viruses as a cause of chronic fatigue before and been wrong.

"This is a very striking initial finding, but it is only an initial finding," says John Coffin, a molecular biologist from Tufts University who was not involved in the study. He co-authored a companion piece about the finding in Science Express.

Researchers have suspected for a long time that chronic fatigue might be caused by a virus.

One reason for that suspicion is that many people get the condition after a flu-like illness, says Mikovits. "They get very bad flu-like symptoms and essentially never recover," she says.

Most viruses don't survive long in the body. But retroviruses are one type that lingers. HIV, for example, is a retrovirus that infects people for a lifetime. So when scientists found XMRV in people a couple of years ago, Mikovits thought there might be a connection to chronic fatigue, which also tends to last a lifetime.

She was in a position to find out. After many years at the National Institutes of Health, she'd come to the Whittemore Peterson Institute, a place founded to help people with chronic fatigue.

Mikovits worked with a team that began checking patients' blood for XMRV. "We simply did a screen of the sickest of the sick of our patients because we figured that would be where we would find the most virus," she says. "And, lo and behold, there it was."

Tests also showed the virus was infectious and was provoking an immune response in people with chronic fatigue.

Isolating The Cause


The finding is "the best news ever" for people with chronic fatigue, says Annette Whittemore, one of the founders of the Whittemore Peterson Institute. "We've always known there was something out there. Now we see its face," she says.

Whittemore has an adult daughter who has had chronic fatigue since she was 12. She created the institute with Dr. Daniel Peterson, one of the first doctors to identify people with the condition that later became known as chronic fatigue syndrome.

Even though XMRV has not yet been shown to cause chronic fatigue syndrome, it has characteristics that make it a likely suspect, experts say.
For one thing, it's a retrovirus.

"Retroviruses in general give rise to infections that persist indefinitely," says Coffin. Most other viruses are eliminated from the body.

Coffin says he's concerned by the finding that nearly 4 percent of healthy people carried XMRV. That would mean 10 million people in the U.S. are infected.

Coffin says scientists need to find out whether the virus is causing health problems other than chronic fatigue in any of these people.

For people who have chronic fatigue, the XMRV finding could lead to the first treatments.

Antiviral drugs developed for people with HIV may also work against XMRV, Mikovits says. The institute plans to begin testing that idea soon.
 

Cort

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"Changing the landscape for diagnosis and possible treatment" - everything just changed!

Not just the Incline Village cohort- the WPI looked at cases all over the US. That's really big - it almost sounds like its been replicated already - since they've tested it so widely. "We found the virus in the same proportion in every outbreak,"

May be able to induce to induce the reactivation of viruses - possibly even viruses found in our DNA -
"This new retrovirus may be able, through infecting human cells, [to] induce a transcription of an endogenous virus,"

Already testing in animals to understand the virus - Animal model testing is already underway

Treatment - Mikovits notes that her team is looking into some reverse transcriptase inhibitors that have already been approved by the U.S. Food and Drug Administration for other uses.

Recently implicated in some severe prostate cancer patients, the retrovirus XMRV has now been found in many with chronic fatigue--changing the landscape for diagnosis and possible treatment

More so than many illnesses, chronic fatigue syndrome (CFS) frustrates those who suffer from it and those close to them, due to its nebulous assembly of symptoms, along with continued controversies over its etiology, diagnosis, treatment and even its nomenclature. Now, the discovery of a familiar retrovirus in many CFS patients could bring new energy to the field—and fresh hope for more specific medical care.

Chronic fatigue is in part a misnomer. The syndrome often has more to do with immune system abnormalities than pervasive tiredness—although the two can go hand in hand. The symptoms range from exhaustion to muscle pain, giving CFS a reputation among some as a "wastebasket diagnosis". The slipperiness of the syndrome is in part because "it's diagnosed based on exclusion," says Judy Mikovits, director of research at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nev., and co-author of research on the retrovirus findings published online today in Science. Doctors often apply the label if no other explanation can be found for a patient's symptoms, which may be part of the reason it seems to pop up in everyone from overworked career women to continually sick children.

Roughly 17 million people worldwide are thought to have CFS, but given current diagnosis methods, the true number could be much higher or lower. Having a specific virus to look for would make for much more robust tests and possibly even be a step toward treatment. Mikovits's team thinks they have found just such a candidate.

The xenotropic murine leukemia virus–related virus (XMRV), a type of gammaretrovirus, has recently been linked to strong cases of prostate cancer. Like CFS, this cancer involves changes in an antiviral enzyme (RNase L). The prostate cancer discovery, described last month by Ila Singh, an associate professor of pathology at the University of Utah in Salt Lake City, et al. in the Proceedings of the National Academy of Sciences (PNAS), along with a traditionally high incidence of cancer in CFS patients, got Mikovits and her team thinking: Would they find the same retrovirus in people with CFS?

After analyzing biological samples from more than 100 CFS patients for the retrovirus, two thirds of them were found to test positive for the virus—compared with 3.7 percent of 218 healthy volunteers who were screened.

To find the retrovirus, Mikovits and her team studied documented cases, such as CFS outbreaks in a symphony orchestra in North Carolina and in Incline Village, Nev. "We found the virus in the same proportion in every outbreak," she says. But how are people getting this retrovirus? "Ila's work shows that everyone's susceptible," Mikovits says of the PNAS paper by Singh that illustrates the link between prostate cancer and XMRV and shows that the virus is not linked to a genetic mutation.

Experiments in Mikovits's lab proved that the retrovirus can be transmitted via blood by infecting healthy cells drawn from volunteers with material from XMRV-positive CFS patients. Mikovits hopes to soon have a better understanding of how the virus might be transferred in the real world, especially among families. If it, for instance, is like human T-lymphotropic virus type 1 (HTLV-1), it may be communicable through breast milk or if it's like a herpes virus that is common in CFS, it may be passed along to offspring.

Precisely how this virus is related to chronic fatigue, however, remains a mystery. One of the problems with tracking down CFS is that it may not be a single ailment. "We think that the problem is that CFS is a collection of many, many different diseases even though it has similar symptoms," says Brigitte Huber, a professor of pathology at Tufts University's Sackler School of Graduate Biomedical Sciences in Boston. She and others suspect that the retrovirus may be unleashing other underlying conditions and viruses in the body.

"This new retrovirus may be able, through infecting human cells, [to] induce a transcription of an endogenous virus," says Huber, who has been studying the presence of an ancient retrovirus (HERV-K18) dormant in most people but active in patients with CFS and multiple sclerosis. "We've already shown that Epstein-Barr virus can do exactly this."

Even in their testing for the XMRV retrovirus, Mikovits says, "We could see a human endogenous virus at the same time" as XMRV. "There are a number of old diseases that seem to be rising at an infectious rate," she says. Although this background noise of various viruses may be difficult to sort though, it brings clues to help researchers find the root cause of CFS. "It's possible, downstream, that this will all feed into the same mechanism," Huber says.

Even before the precise mechanisms are found, work toward finding treatment proceeds. Animal model testing is already underway, and Mikovits notes that her team is looking into some reverse transcriptase inhibitors that have already been approved by the U.S. Food and Drug Administration for other uses.

"Now we have a drug target and a marker," Mikovits says. "If we treat them with a drug and they get better, we win."

In the meantime, her team has been making quick strides toward a simple diagnostic test that doctors could use to check for the virus. Tests have been running smoothly in the lab, she notes, with some diagnostics companies already interested in the technology. She predicts a test will be available in less than six months. Mikovits adds that she is "excited that we will actually have some causes…rather than just building a better wheelchair."
 

Mary

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Thanks for all the info

but I don't know whether to be sad or glad about this news. I had been pinning my hopes on getting my methylation cycle jumpstarted, have made small improvements, so the idea of having to deal with a retrovirus and all that entails (antivirals etc. which I can't tolerate) is actually rather discouraging to me.

Yes, it's good to have biomarker etc., so we'll be taken seriously, but what a biomarker! I'd rather it was something else ...

Mary
 

Dolphin

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Thanks Rich.

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"
CFS is much more like a chronic viral disease than most chronic diseases, in case WCR didn't notice!

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.
If they use the "empirical" definition, they won't replicate it. :(
 

Frickly

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It's a good day...

However, I do have to agree with Mary above. Does this mean we will never get better? Will there never be a cure? Will we all die early from different diseases because of our weakened immune system? Have I given this virus to my kids? My husband?

Sorry to be a downer as I am very excited about this news but have mixed feelings about it's implications.
 

Dolphin

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However, I do have to agree with Mary above. Does this mean we will never get better? Will there never be a cure? Will we all die early from different diseases because of our weakened immune system? Have I given this virus to my kids? My husband?

Sorry to be a downer as I am very excited about this news but have mixed feelings about it's implications.
In some ways, nothing has changed from yesterday. The vast vast majority of young children of people with the illness I see are healthy. Similarly with partners.

People aren't going to die any earlier than they were yesterday. It doesn't mean people have AIDS.
 

Kati

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If 2/3 of CFS test positive for the virus, well what about the rest of them ? Does that mean they don't have the disease? Or perhaps they haven't found the virus but it's there- or latent-

It's wonderful news for the ME/CFS community, but I wonder how long it will take till everyone in the communities get tested and treated-

Another question I have is the virus is known to cause an aggressive type of prostate cancer- how about women? I guess we get ME/CFS- but is it associated with other types of maligancies?

So much more to be discovered- I hope that we get access to all the retroviral medications soon and also that we get recognition from CDC and especially insurance companies.

Now it makes me think why so many nurses get sick with CFIDS- I have had a few needlestick injuries in my carreer, saliva contact and blood droplets in the eyes. That would qualify me for WCB- in theory.
 
K

_Kim_

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Thanks to Cort and others for the news

Yet, I agree with Mary and Fickly. The news is not something to be so thrilled about on a personal level. There is a sick feeling in the pit of my stomach. Not only for my own future, but for those that I may have unknowingly infected. I thought I was being careful and responsible by getting tested for HIV before having unprotected sex with my boyfriend.
 

Kati

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It means that instead of being labelled as a psychosomatic disease, we now have a potential cause for this disease, and potentially many posible treatments.It also means that the governments hopefully will release the purse strings for more research on CFIDS, and more researchers will be interested by this discovery.

Indeed we will likely be the same tomorrow- still in bed, and dizzy and short of breath, sore throat etc... But we are better off knowing what we are dealing with then being left in the dark (no pun intended) and marginalized by the society. This is about social recognition, validation and treatments of more of us.

If we have a virus resembling HIV, I have to say that many out there live a very normal life, with control of the disease by medication, but they can work, walk, run, travel, and enjoy life.

Thank you W-P institute. Keep up the wonderful work.



However, I do have to agree with Mary above. Does this mean we will never get better? Will there never be a cure? Will we all die early from different diseases because of our weakened immune system? Have I given this virus to my kids? My husband?

Sorry to be a downer as I am very excited about this news but have mixed feelings about it's implications.
 

InvertedTree

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Thanks for the information Cort

I know that doctors' who work with HIV patients have been able to suppress the HIV virus with the use of anti retro-viral medications making it virutally undetectable.

I wonder if the same medications can suppress this virus?

It's interesting because my primary care doctor is also an HIV doctor. He doesn't believe in CFS but thought that my symptoms were due to some sort of retrovirus.

I'm going to download the article and bring it to him and see if he'd be willing to try some of the anti retro viral meds.