Vincent C. Lombardi, Francis W. Ruscetti, Jaydip Das Gupta, Max A. Pfost, Kathryn S. Hagen, Daniel L. Peterson, Sandra K. Ruscetti, Rachel K. Bagni, Cari Petrow-Sadowski, Bert Gold, Michael Dean, Robert H. Silverman, Judy A. Mikovits
Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines following exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.
The following is a Q&A fromThe Whittemore Peterson InstituteWhat 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.
Is XMRV airborne? No, retroviruses are not traditionally airborne viruses. However, since XMRV is a blood borne retrovirus, it may be possible to transmit through sexual contact, sharing needles, blood transfusions, and breastfeeding. Sharing household items like toothbrushes, razors, or items that come into contact with blood is not recommended as a precautionary measure. Is there a test available for XMRV? I think I have ME/CFS or have been diagnosed with this.
The WPI has developed a blood test for the detection of XMRV. The test is currently undergoing clinical evaluation and validation. We hope to have a clinical test available to the public within the year.
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.
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.
Are there federal guidelines for dealing with XMRV? Guidelines will be established as more is leaned about XMRV.
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.
Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines following exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.
The following is a Q&A fromThe Whittemore Peterson Institute
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.
Is XMRV airborne?
No, retroviruses are not traditionally airborne viruses. However, since XMRV is a blood borne retrovirus, it may be possible to transmit through sexual contact, sharing needles, blood transfusions, and breastfeeding. Sharing household items like toothbrushes, razors, or items that come into contact with blood is not recommended as a precautionary measure. Is there a test available for XMRV? I think I have ME/CFS or have been diagnosed with this.
The WPI has developed a blood test for the detection of XMRV. The test is currently undergoing clinical evaluation and validation. We hope to have a clinical test available to the public within the year.
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.
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.
Are there federal guidelines for dealing with XMRV?
Guidelines will be established as more is leaned about XMRV.
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.