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Source link: http://jvi.asm.org/c.../JVI.00693-11v1


Absence of XMRV and other MLV-related viruses in patients with Chronic Fatigue Syndrome
Clifford H. Shin¹, Lucinda Bateman², Robert Schlaberg¹, Ashley M. Bunker³, Christopher J. Leonard¹, Ronald W. Hughen⁴, Alan R. Light⁴, Kathleen C. Light⁴, and Ila R. Singh^{1,* 1} Department of Pathology, University of Utah, Salt lake City, Utah, 84112
² Fatigue Consultation Clinic, Salt Lake City, Utah, 84102
³ ARUP Laboratories, Salt Lake City, Utah, 84108
⁴ Department of Anesthesiology, University of Utah, Salt Lake City, Utah, 84112

^* Corresponding author: Mailing address: Emma Eccles Jones Medical Research Building, Department of Pathology, 15 North Medical Drive East, Suite #2100, Salt Lake City, UT 84112, Phone: (801) 213-3737, Fax: (801) 585-7376, Email: ila.singh@path.utah.edu

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ABSTRACT Chronic fatigue syndrome (CFS) is a multi-system disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blinded manner using molecular, serological and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS. We did not find XMRV or related MLVs, either as viral sequences or infectious virus, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV-related viruses including XMRV and off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.

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C.D.D.

[Zac]

Source Link: http://www.meassocia....org.uk/?p=6030


Whittemore Peterson Institute response to the Ila Singh paper, 9 May 2011
by tonybritton on May 10, 2011 While WPI researchers continue to review the data presented by Dr. Singh, we believe that it is important to correct and clarify information regarding this study. Several individuals were consented to participate in this study as positive controls to enable Dr. Singh to develop assays to detect multiple variants of XMRV. Of these, only three were from the original Lombardi et al. cohort, two of whom were among those positive for a XMRV. A XMRV was isolated from one of those patient’s PBMCs, cloned and fully sequenced (GenBank® accession number GQ 497343 as identified in the NIH genetic sequence database). Sequence data demonstrates that this virus is clearly distinct from XMRV (vp62) and 22Rv1. A budding virus particle from that sample was pictured in an electron micrograph in Lombardi et al. Virus from that patient sample was also transmitted both from the PBMCs and plasma to an uninfected indicator cell line, LNCaP. Finally, these results were supported by a separate lab using serological methods as reported by Lombardi et al.

Twelve additional samples from individuals not included in the Lombardi et al. study were independently collected by a third party and sent directly to Dr. Singh’s lab. Some of these subjects were positive for highly related sequences, including the polytropic and modified polytropic sequences identified by Lo et al., as determined by the WPI prior to the publication of the Singh study. Many of those subjects were also positive for ENV antibodies to a XMRV (vp62 and other XMRV family members), indicating that these patients had an immune response to a XMRV.

In addition, WPI investigators and others have provided evidence of sequence diversity between a XMRV (vp62), other similar XMRVs detected by WPI (designated internally with a number corresponding to a clinical isolate), a XMRV (p variant), and other related human gamma retroviruses. Therefore, we believe that it is vitally important that investigators interested in furthering the understanding of blood borne XMRV as a human pathogen use a proven positive clinical isolate as the control when developing tests to detect this newly discovered human retrovirus.

WPI and the U.S. clinical laboratory performing XMRV tests pursuant to a license agreement with WPI have extensive controls in place to prevent and detect contamination. Approximately three thousand tests have been performed on patient samples to date using clinically validated tests; about one third have been found to be positive. Multiple sequences from these three thousand samples have been submitted to GenBank® and are awaiting publication. It is critical, in light of these findings, that all treatment decisions are left to physicians and their patients, including the use of antiretrovirals.

While WPI researchers acknowledge that there is still much to be learned about the lifecycle and in vivo reservoirs of this family of human gamma retroviruses, we remain confident in the results reported in Science by Lombardi et al. Most importantly, we are committed to human gamma retroviral research in neuro-immune disease and will continue to offer our help to the medical and scientific community when requested.