Mystery Virus Still Keeping Secrets
By Michael Smith, North American Correspondent, MedPage TodayPublished: October 13, 2010Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine.
"And in Europe, Frater and colleagues studied 133 people with chronic HIV infection, 101 with an acute HIV infection, and 67 with hepatitis C from cohorts in England and Switzerland, using a variety of testing methods on plasma or peripheral blood mononuclear cells.
But none of the samples contained XMRV, they reported."
The mysterious retrovirus recently associated with prostate cancer and chronic fatigue syndrome remains ... mysterious. That's the upshot of three papers describing attempts to pin down the xenotropic murine leukemia virus-related virus -- XMRV for short -- in the Nov. 15 issue of the Journal of Infectious Diseases.
The virus was first linked with prostate cancer in 2006 after investigators found it in a subset of patients with a genetic variant that impairs innate immune responses to viral infection. Because people with chronic fatigue syndrome have the same variant, researchers also looked for -- and found -- XMRV in a cohort of such patients.But confirmation has been hard to come by and indeed, the three current studies found conflicting data:
Researchers led by Jason Kimata, PhD, of Baylor College of Medicine in Houston found the virus in 22% of a cohort of 144 prostate cancer patients, but no association with the gene variant that affects immunity.
Investigators led by John Frater, MBBS, PHD, of Oxford University, found no sign of the virus in 230 patients with either HIV or hepatitis C.
And a team led by Athe Tsibris, MD, of Massachusetts General Hospital, didn't detect the virus in a cohort of patients with chronic fatigue syndrome or chronic immunomodulatory conditions, such as HIV or rheumatoid arthritis.
Note that the editorialists from the National Cancer Institute do not feel that the current state of research justifies any attempts at therapeutic internvention aimed at XMRV infection.The absence of a pattern may be the result of a range of factors, including such things as geographic distribution, patient selection, the type of sample being analyzed, and the way the virus is detected, according to Mary Kearney, PhD, and Frank Maldarelli, MD, PhD, both of the National Institutes of Health.
For example, they noted in an accompanying editorial, Tsibris and colleagues found no sign of XMRV in a cohort of patients with chronic fatigue syndrome in Boston, but the original discovery of the association was made in a different geographical region.
The studies highlight the need for ways to resolve the conflicting reports, Kearney and Maldarelli argued, including:
Standard ways of detecting the virus
Prospective epidemiological studies
Sharing of reagents and samples among researchers
Better understanding of the evolution of the virus and its close relatives
Developing animal models
In the main paper in the journal, Kimata and colleagues looked for the so-called R462Q polymorphism in the gene RNASEL, as well as for XMRV, in a retrospective cohort of patients in the southern U.S.
They found the R462Q polymorphism in about a third of all RNASEL alleles, and XMRV in normal or prostate cancer tissue of 32 of the 144 patients.
But, they reported, a positive result for XMRV wasn't significantly correlated with the presence of the polymorphism.
Also, the researchers had both normal and cancerous prostate tissue available for 57 patients and, in that group, they found XMRV in 36.8% of the normal tissue samples and 43.9% of the cancer samples. Three patients only had the virus in normal tissue and seven only had it in the cancer cells, they reported, "suggesting that XMRV does not specifically target tumor tissue in the prostate."
Kimata and colleagues concluded that the results confirm that the virus can be found in prostate cancer patients in the U.S., although large studies elsewhere in the world have failed to detect it, but the population at risk is larger than just those with two copies of the R462Q polymorphism.
The researchers in Boston also investigated the role of immunocompromise, studying 32 people with chronic fatigue syndrome, 43 with HIV, 97 with rheumatoid arthritis, 26 with either a hematopoietic stem-cell or solid organ transplant, and 95 from a general cohort of patients presenting for medical care.
But despite a testing method sensitive enough to detect two copies of XMRV in 200 nanograms of peripheral blood mononuclear cell DNA, they found no evidence of the virus even in those with chronic fatigue syndrome.
And in Europe, Frater and colleagues studied 133 people with chronic HIV infection, 101 with an acute HIV infection, and 67 with hepatitis C from cohorts in England and Switzerland, using a variety of testing methods on plasma or peripheral blood mononuclear cells.
But none of the samples contained XMRV, they reported.
The finding suggests that if the virus is present in Europe, it is not spread by either sexual or bloodborne routes, they concluded.
It's premature to start thinking about therapies for XMRV infection, Kearney and Maldarelli argued, despite in vitro evidence that the virus is susceptible to some drugs.
"There are calls for use of antiretroviral agents for therapy," they noted, but that would be "premature and medically indefensible" outside a clinical trial.
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