Tag: XMRV

Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Detection of a retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), has recently been reported in 67% of patients with chronic fatigue syndrome. We have studied a total of 170 samples from chronic fatigue syndromepatients from two UK cohorts and 395 controls for evidence of XMRV infection by looking either for the presence of viral nucleic acids using quantitative PCR (limit of detection <16 viral copies) or for the presence of serological responses using a virus neutralisation assay.

RESULTS: We have not identified XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient. Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses. Four positive samples were specific for XMRV.

CONCLUSIONS: No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human serum samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes.

 

Source: Groom HC, Boucherit VC, Makinson K, Randal E, Baptista S, Hagan S, Gow JW, Mattes FM, Breuer J, Kerr JR, Stoye JP, Bishop KN. Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. Retrovirology. 2010 Feb 15;7:10. doi: 10.1186/1742-4690-7-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839973/ (Full article)

 

Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome

Abstract:

BACKGROUND: In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer. This finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. We have investigated CFS sufferers in the UK to determine if they are carriers of XMRV.

METHODOLOGY: Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS. DNA extracted from blood samples of 186 CFS patients were screened for XMRV provirus and for the closely related murine leukaemia virus by nested PCR using specific oligonucleotide primers. To control for the integrity of the DNA, the cellular beta-globin gene was amplified. Negative controls (water) and a positive control (XMRV infectious molecular clone DNA) were included. While the beta-globin gene was amplified in all 186 samples, neither XMRV nor MLV sequences were detected.

CONCLUSION: XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.

 

Source: Erlwein O, Kaye S, McClure MO, Weber J, Wills G, Collier D, Wessely S, Cleare A. Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS One. 2010 Jan 6;5(1):e8519. doi: 10.1371/journal.pone.0008519. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795199/ (Full article)

 

Of Mice and Men: On the Origin of XMRV

Abstract:

The novel human retrovirus xenotropic murine leukemia virus-related virus (XMRV) is arguably the most controversial virus of this moment. After its original discovery in prostate cancer tissue from North American patients, it was subsequently detected in individuals with chronic fatigue syndrome from the same continent. However, most other research groups, mainly from Europe, reported negative results.

The positive results could possibly be attributed to contamination with mouse products in a number of cases, as XMRV is nearly identical in nucleotide sequence to endogenous retroviruses in the mouse genome. But the detection of integrated XMRV proviruses in prostate cancer tissue proves it to be a genuine virus that replicates in human cells, leaving the question: how did XMRV enter the human population?

We will discuss two possible routes: either via direct virus transmission from mouse to human, as repeatedly seen for, e.g., Hantaviruses, or via the use of mouse-related products by humans, including vaccines. We hypothesize that mouse cells or human cell lines used for vaccine production could have been contaminated with a replicating variant of the XMRV precursors encoded by the mouse genome.

 

Source: van der Kuyl AC, Cornelissen M, Berkhout B. Of Mice and Men: On the Origin of XMRV. Front Microbiol. 2011 Jan 17;1:147. doi: 10.3389/fmicb.2010.00147. ECollection 2010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109487/ (Full article)

 

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome

Abstract:

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%) as 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 after their 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.

Comment in:

Erratum in: Partial retraction. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. [Science. 2011]

Retraction in: Retraction. [Science. 2011]

 

Source: Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009 Oct 23;326(5952):585-9. doi: 10.1126/science.1179052. Epub 2009 Oct 8. http://science.sciencemag.org/content/326/5952/585.long (Full article)

 

Virology. A new virus for old diseases?

There is little consensus in the medical community on whether chronic fatigue syndrome is a distinct disease. As its name implies, the condition is characterized by debilitating fatigue persisting for many years, and it affects as much as 1% of the world’s population. Although chronic inflammation is often found in these patients, no infectious or toxic agent has been clearly implicated in this disease, which is diagnosed largely by excluding other conditions that cause similar symptoms (1). In this week’s Science Express, Lombardi et al. (2) describe the detection of xenotropic murine leukemia virus–related virus (XMRV) in about two-thirds of patients diagnosed with chronic fatigue syndrome. Both laboratory and epidemiological studies are now needed to determine whether this virus has a causative role, not only in this disease, but perhaps in others as well.

Chronic fatigue syndrome is not the first human disease to which XMRV has been linked. The virus first was described about 3 years ago in a few prostate cancer patients (3), and recently detected in nearly a quarter of all prostate cancer biopsies (4). It has been isolated from both prostate cancer and chronic fatigue syndrome patients, and is similar to a group of endogenous murine leukemia viruses (MLVs) found in the genomes of inbred and related wild mice. Although a half century of studies on MLVs and other gammaretroviruses have led to important discoveries on which much of our current understanding of cancer rests, there has been no clear evidence demonstrating human infection with gammaretroviruses, or associating these agents with any human disease.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818280/

Comment on: Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. [Science. 2009]

 

Source: Coffin JM, Stoye JP. Virology. A new virus for old diseases? Science. 2009 Oct 23;326(5952):530-1. doi: 10.1126/science.1181349. Epub 2009 Oct 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818280/ (Full article)