Category: Viruses

Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study

Abstract:

Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody. Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement, and reactivity was similar among CFS subjects and negative controls. These results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted.

 

Source: Simmons G, Glynn SA, Komaroff AL, Mikovits JA, Tobler LH, Hackett J Jr, Tang N, Switzer WM, Heneine W, Hewlett IK, Zhao J, Lo SC, Alter HJ, Linnen JM, Gao K, Coffin JM, Kearney MF, Ruscetti FW, Pfost MA, Bethel J, Kleinman S, Holmberg JA, Busch MP; Blood XMRV Scientific Research Working Group (SRWG). Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study. Science. 2011 Nov 11;334(6057):814-7. doi: 10.1126/science.1213841. Epub 2011 Sep 22. Collaborators (25) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299483/ (Full article)

 

No detectable XMRV in subjects with chronic fatigue syndrome from Quebec

Abstract:

We investigated the presence of XMRV in a cohort of Quebec patients with chronic fatigue syndrome (CFS). DNA was purified from activated peripheral blood mononuclear cells (PBMCs) and PCR was used to detect XMRV gag and env in 72 patients. Anti-XMRV antibodies were searched in sera of 62 patients by Western blot analysis. Attempts to detect XMRV antigens was made, using immunofluorescence with Gag anti-p30 antiserum on activated PBMC from 50 patients. Plasma viremia was measured by RT-PCR on 9 subjects. Finally, detection of infectious virus in 113 CFS subjects was made by co-culture of PHA+IL-2 activated PBMC with human LNCaP carcinoma cells, and by infecting the same susceptible cells with plasma, using a reverse transcriptase (RT) assay as a readout in both experiments. No detection of XMRV footprints nor infectious virus was detected with any of the approaches, in any of the tested individuals.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Cool M, Bouchard N, Massé G, Laganière B, Dumont A, Hanna Z, Phaneuf D, Morisset R, Jolicoeur P. No detectable XMRV in subjects with chronic fatigue syndrome from Quebec. Virology. 2011 Nov 10;420(1):66-72. doi: 10.1016/j.virol.2011.08.018. Epub 2011 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/21925693

 

Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored peripheral blood mononuclear cell (PBMC) samples were tested with 3 separate polymerase chain reaction (PCR) assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins was positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a follow-up plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Jerome KR, Diem K, Huang ML, Selke S, Corey L, Buchwald D.Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome. Diagn Microbiol Infect Dis. 2011 Sep;71(1):66-71. doi: 10.1016/j.diagmicrobio.2011.06.003. Epub 2011 Jul 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158821/ (Full article)

 

Chronic fatigue syndrome, the immune system and viral infection

Abstract:

The chronic fatigue syndrome (CFS), as defined by recent criteria, is a heterogeneous disorder with a common set of symptoms that often either follows a viral infection or a period of stress. Despite many years of intense investigation there is little consensus on the presence, nature and degree of immune dysfunction in this condition.

However, slightly increased parameters of inflammation and pro-inflammatory cytokines such as interleukin (IL) 1, IL6 and tumour necrosis factor (TNF) α are likely present. Additionally, impaired natural killer cell function appears evident. Alterations in T cell numbers have been described by some and not others.

While the prevalence of positive serology for the common herpes viruses appears no different from healthy controls, there is some evidence of viral persistence and inadequate containment of viral replication. The ability of certain herpes viruses to impair the development of T cell memory may explain this viral persistence and the continuation of symptoms. New therapies based on this understanding are more likely to produce benefit than current methods.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012 Jan;26(1):24-31. doi: 10.1016/j.bbi.2011.06.016. Epub 2011 Jul 2. https://www.ncbi.nlm.nih.gov/pubmed/21756995

 

No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected

Abstract:

Members of the gammaretroviruses–such as murine leukemia viruses (MLVs), most notably XMRV [xenotropic murine leukemia virus (X-MLV)-related virus–have been reported to be present in the blood of patients with chronic fatigue syndrome (CFS).

We evaluated blood samples from 61 patients with CFS from a single clinical practice, 43 of whom had previously been identified as XMRV-positive. Our analysis included polymerase chain reaction and reverse transcription polymerase chain reaction procedures for detection of viral nucleic acids and assays for detection of infectious virus and virus-specific antibodies.

We found no evidence of XMRV or other MLVs in these blood samples. In addition, we found that these gammaretroviruses were strongly (X-MLV) or partially (XMRV) susceptible to inactivation by sera from CFS patients and healthy controls, which suggested that establishment of a successful MLV infection in humans would be unlikely. Consistent with previous reports, we detected MLV sequences in commercial laboratory reagents. Our results indicate that previous evidence linking XMRV and MLVs to CFS is likely attributable to laboratory contamination.

Comment in: Prostate cancer: XMRV–contaminant, not cause? [Nat Rev Urol. 2011]

 

Source: Knox K, Carrigan D, Simmons G, Teque F, Zhou Y, Hackett J Jr, Qiu X, Luk KC, Schochetman G, Knox A, Kogelnik AM, Levy JA. No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected. Science. 2011 Jul 1;333(6038):94-7. doi: 10.1126/science.1204963. Epub 2011 May 31. https://www.ncbi.nlm.nih.gov/pubmed/21628393

 

Xenotropic murine leukemia virus-related virus-associated chronic fatigue syndrome reveals a distinct inflammatory signature

Abstract:

BACKGROUND: The recent identification of xenotropic murine leukemia virus-related virus (XMRV) in the blood of patients with chronic fatigue syndrome (CFS) establishes that a retrovirus may play a role in the pathology in this disease. Knowledge of the immune response might lead to a better understanding of the role XMRV plays in this syndrome. Our objective was to investigate the cytokine and chemokine response in XMRV-associated CFS.

MATERIALS AND METHODS: Using Luminex multi-analyte profiling technology, we measured cytokine and chemokine values in the plasma of XMRV-infected CFS patients and compared these data to those of healthy controls. Analysis was performed using the Gene Expression Pattern Analysis Suite and the Random Forest tree classification algorithm.

RESULTS: This study identifies a signature of 10 cytokines and chemokines which correctly identifies XMRV/CFS patients with 93% specificity and 96% sensitivity.

CONCLUSION: These data show, for the first time, an immunological pattern associated with XMRV/CFS.

 

Source: Lombardi VC, Hagen KS, Hunter KW, Diamond JW, Smith-Gagen J, Yang W, Mikovits JA. Xenotropic murine leukemia virus-related virus-associated chronic fatigue syndrome reveals a distinct inflammatory signature. In Vivo. 2011 May-Jun;25(3):307-14. https://www.ncbi.nlm.nih.gov/pubmed/21576403

 

XMRV, prostate cancer and chronic fatigue syndrome

Abstract:

BACKGROUND: A new retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), was identified in 2006 and an association was claimed between it and a genetic polymorphism predisposing to cancer of the prostate. In 2009 the same virus was identified in a cohort of patients with chronic fatigue syndrome (CFS). In 2010 a second related virus was identified in a separate group of CFS patients. A series of studies from disparate geographical areas have failed to substantiate this work. Most recently several papers have suggested that the detection of these viruses was explained by laboratory contamination.

SOURCES OF DATA: All papers including the wording XMRV were abstracted from the NIH library of medicine database and included in the analysis.

AREAS OF AGREEMENT: XMRV is a newly described retrovirus whose nucleic acid has been identified in samples from patients with both prostate cancer and CFS.

AREAS OF CONTROVERSY: Opinions differ as to whether the detected nucleic acid indicates infection with this virus in this disease or whether laboratory contamination of samples accounts for its presence.

GROWING POINTS: An increasing number of papers now refute the association of XMRV with human disease in humans although there is some evidence of serological reactivity to the virus. While it is unlikely that XMRV is a major cause of either prostate cancer or CFS, it can infect human cells and might yet have a role in human disease.

AREAS TIMELY FOR DEVELOPING RESEARCH: Further studies to either prove or disprove the disease association of the virus are ongoing.

 

Source: Kenyon JC, Lever AM. XMRV, prostate cancer and chronic fatigue syndrome. Br Med Bull. 2011;98:61-74. doi: 10.1093/bmb/ldr010. Epub 2011 May 6. https://www.ncbi.nlm.nih.gov/pubmed/21551158

 

Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a multisystem 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 blind manner using molecular, serological, and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS patients. We did not find XMRV or related MLVs either as viral sequences or infectious viruses, 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 the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.

 

Source: Shin CH, Bateman L, Schlaberg R, Bunker AM, Leonard CJ, Hughen RW, Light AR, Light KC, Singh IR. Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome. J Virol. 2011 Jul;85(14):7195-202. doi: 10.1128/JVI.00693-11. Epub 2011 May 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126563/ (Full article)

 

Chronic fatigue syndrome, XMRV and blood safety

Abstract:

In the past few months, there has been public discussion relating to a new perspective on blood safety and specifically upon measures to prevent or discourage donation by individuals with a diagnosis of myalgic encephalopathy-chronic fatigue syndrome. This reflects an intriguing interplay between science, public health and public concern and illustrates some of the difficulties of making decisions in the face of uncertainty and inadequate information.

 

Source: Dodd RY. Chronic fatigue syndrome, XMRV and blood safety. Future Microbiol. 2011 Apr;6(4):385-9. doi: 10.2217/fmb.11.24. https://www.ncbi.nlm.nih.gov/pubmed/21526940

 

XMRV as a human pathogen?

Abstract:

Xenotropic murine leukemia virus-related virus (XMRV) has been proposed to be associated with prostate cancer and chronic fatigue syndrome (CFS). This proposition has been controversial because many investigators have failed to replicate the reported associations. Here, we explore whether XMRV is an authentic human pathogen in the light of recent findings that indicate otherwise.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Wainberg MA, Jeang KT. XMRV as a human pathogen? Cell Host Microbe. 2011 Apr 21;9(4):260-2. doi: 10.1016/j.chom.2011.04.001. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551452/ (Full article)