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More studies find no XMRV in CFS, HIV, or hepatitis C

Saturday 23 October 2010

XMRVFrom MedScape (via Co-Cure):

More studies find no XMRV in chronic fatigue syndrome, HIV, or hepatitis C

A ProMED-mail post
(ProMED-mail is a program of the International Society for Infectious Diseases)

Date: Wed 20 Oct 2010
Source: Medscape Infectious Diseases, Medical News [summ., edited]

Another US study has failed to detect xenotropic murine leukemia virus-related virus (XMRV) in the blood of patients with chronic fatigue syndrome (CFS) or others with immune dysfunction, and investigators of a separate European study also found no evidence of this retrovirus in patients infected with HIV [human immunodeficiency virus] or hepatitis C virus. Both studies were published online 11 Oct 2010 and will appear in the 15 Nov 2010 print issue of the Journal of Infectious Diseases.

The negative findings come just weeks after publication of a study that was the 2nd to find a murine leukemia-type virus in patients with CFS (Proc Natl Acad Sci USA. 2010; 107(36):15874-9;) [see also ProMED-mail Chronic fatigue syndrome: murine retroviruses link? 20100825.2986]. That work used the same primers for polymerase chain reaction (PCR) amplification as used in the current US study, write the authors, led by Athe Tsibris, MD, from the Division of Infectious Diseases at Massachusetts General Hospital, Boston. Dr Tsibris' group also reportedly used the same sensitive PCR methods as those of Lombardi and colleagues, who first reported XMRV in patients with CFS a year ago (Science. 2009; 326:585-9;).

"[Our finding] suggests that differences in PCR techniques from study to study do not explain the disparate results seen in XMRV studies of chronic fatigue syndrome," Dr Tsibris said in a press release from the Infectious Diseases Society of America, publisher of the Journal of Infectious Diseases.

Dr Tsibris and colleagues suggested that "geographical clustering of XMRV infection" could explain why other investigators found XMRV in patients with CFS. Their group, from Boston, tested peripheral blood mononuclear cells of 293 patients from academic hospitals. Of the participants, 23 met the Centers for Disease Control and Prevention revised case definition of CFS, and 95 were from a general cohort of patients who received medical care, which could have included healthy individuals seeking routine care, according to the authors.

All other participants had chronic conditions with altered immune function: 43 with HIV, 97 with rheumatoid arthritis, and 26 who had undergone solid-organ or hematopoietic stem cell transplantation.

The authors reported that they did not detect XMRV DNA in any samples. They did detect a mouse endogenous retroviral sequence in one participant's blood, but because they could not replicate that finding, the authors attributed it to contamination from an unidentified source.

Despite the number of studies that have been unable to find an association between XMRV and CFS, Dr Tsibris told Medscape Medical News that it is too early to discount an association. "Additional next steps that would be helpful would be a standardized, cross-validated assay for XMRV detection in clinical samples," he said, "so that we can all at least agree on what a positive XMRV test actually is, and a blinded multilaboratory comparison of XMRV testing from CFS and control samples." The National Institutes of Health has plans for a study like this, according to Dr Tsibris.

In the other study in the Journal of Infectious Diseases, UK and Swiss researchers aimed to determine whether patients with HIV type 1 or hepatitis C virus infection were at increased risk for XMRV infection. Led by Eleanor Barnes, MD, from Oxford University's Department of Clinical Medicine, United Kingdom, the authors tested 230 patients: 84 with chronic HIV infection, 79 with acute HIV infection, and 67 with hepatitis C virus infection.

After being unable to detect XMRV in plasma or peripheral blood mononuclear cells using PCR in any of the patients, the researchers retested 64 patients using a T-cell enzyme-linked immunospot (ELISPOT) assay. Of the 49 patients with acute HIV infection and 14 patients infected with hepatitis C virus whose peripheral blood samples were assayed, none were positive for XMRV, the authors report.

"Although [they are] widely used to detect T cells targeting retroviral peptides, this is the 1st time ELISPOT assays have been applied for the detection of responses to XMRV," the authors write. "Patient cells were responsive to other antigens, suggesting that the lack of responses simply reflects an absence of XMRV Gag-specific T cells in our cohort."

Given their findings, Dr Barnes said in a press release that "if XMRV is a human pathogen, it is not enriched in the blood of patients with HIV or hepatitis C virus, and by implication it is unlikely to be spread through sexual or blood-borne routes in the United Kingdom and Western Europe."

The possibility that XMRV can be transmitted through blood arose after Lombardi and coworkers reported that they could secondarily transmit the virus from the blood cells and plasma of infected patients with CFS. This led the transfusion medicine organization AABB to recommend earlier this year [2010] that blood collection centers discourage people with a diagnosis of CFS or related disorder from donating blood or blood components.

A 3rd study in the Journal of Infectious Diseases reported finding XMRV in patients with prostate cancer, as some other researchers have found.

The conflicting results of the 3 studies led authors of an accompanying editorial to subtitle their commentary "Reach for a Scorecard, Not a Prescription Pad." Mary Kearney, PhD, and Frank Maldarelli, PhD, MD, from the HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, point out in the editorial that valid detection of XMRV remains an ongoing problem.

[Byline: Kathleen Louden]

-- Communicated by:
[log in to unmask]

[In the accompanying editorial Mary Kearney and Frank Maldarelli suggest that the following steps will be necessary to resolve this controversy: (1) standardization of detection assays, (2) prospective epidemiologic surveys, (3) sharing of reagents and samples, (4) design of "comprehensive and rigorous" phylogenetic sequence analyses, and (5) development of "tractable animal models," such as macaques. Such models will be necessary to dissect XMRV pathogenesis. "Only when this is done in a rigorous fashion will it become clear what role XMRV or related viruses have in human disease."

ProMED-mail will await resolution of this controversy before reporting further developments in this field.

Images of XMRV can be viewed at - Mod.CP]

The above originally appeared here.


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