Tag: XMRV

Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions

Abstract:

We investigated the prevalence of xenotropic murine leukemia virus-related virus (XMRV) among 293 participants seen at academic hospitals in Boston, Massachusetts. Participants were recruited from the following 5 groups of patients: chronic fatigue syndrome (n = 32), human immunodeficiency virus infection (n = 43), rheumatoid arthritis (n = 97), hematopoietic stem-cell or solid organ transplant (n = 26), or a general cohort of patients presenting for medical care (n = 95). XMRV DNA was not detected in any participant samples. We found no association between XMRV and patients with chronic fatigue syndrome or chronic immunomodulatory conditions.

Comment in: Current status of xenotropic murine leukemia virus-related retrovirus in chronic fatigue syndrome and prostate cancer: reach for a scorecard, not a prescription pad. [J Infect Dis. 2010]

 

Source: Henrich TJ, Li JZ, Felsenstein D, Kotton CN, Plenge RM, Pereyra F, Marty FM, Lin NH, Grazioso P, Crochiere DM, Eggers D, Kuritzkes DR, Tsibris AM. Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions. J Infect Dis. 2010 Nov 15;202(10):1478-81. doi: 10.1086/657168. Epub 2010 Oct 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957553/ (Full article)

 

Distribution of xenotropic murine leukemia virus-related virus (XMRV) infection in chronic fatigue syndrome and prostate cancer

Abstract:

In 2006, sequences described as xenotropic murine leukemia virus-related virus (XMRV) were discovered in prostate cancer patients. In October 2009, we published the first direct isolation of infectious XMRV from humans and the detection of infectious XMRV in patients with chronic fatigue syndrome. In that study, a combination of classic retroviral methods were used including: DNA polymerase chain reaction and reverse transcriptase polymerase chain reaction for gag and env, full length genomic sequencing, immunoblotting for viral protein expression in activated peripheral blood mononuclear cells, passage of infectious virus in both plasma and peripheral blood mononuclear cells to indicator cell lines, and detection of antibodies to XMRV in plasma. A combination of these methods has since allowed us to confirm infection by XMRV in 85% of the 101 patients that were originally studied.

Since 2009, seven studies, predominantly using DNA polymerase chain reaction of blood products or tumor tissue, have reported failures to detect XMRV infection in patients with either prostate cancer or chronic fatigue syndrome. A review of the current literature on XMRV supports the importance of applying multiple independent techniques in order to determine the presence of this virus. Detection methods based upon the biological and molecular amplification of XMRV, which is usually present at low levels in unstimulated blood cells and plasma, are more sensitive than assays for the virus by DNA polymerase chain reaction of unstimulated peripheral blood mononuclear cells.

When we examined patient blood samples that had originally tested negative by DNA polymerase chain reaction by more sensitive methods, we observed that they were infected with XMRV; thus, the DNA polymerase chain reaction tests provided false negative results.

Therefore, we conclude that molecular analyses using DNA from unstimulated peripheral blood mononuclear cells or from whole blood are not yet sufficient as stand-alone assays for the identification of XMRV-infected individuals. Complementary methods are reviewed, that if rigorously followed, will likely show a more accurate snapshot of the actual distribution of XMRV infection in humans.

 

Source: Mikovits JA, Huang Y, Pfost MA, Lombardi VC, Bertolette DC, Hagen KS, Ruscetti FW. Distribution of xenotropic murine leukemia virus-related virus (XMRV) infection in chronic fatigue syndrome and prostate cancer. AIDS Rev. 2010 Jul-Sep;12(3):149-52. https://www.ncbi.nlm.nih.gov/pubmed/20842203

 

Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Recent controversy has surrounded the question of whether xenotropic murine leukaemia virus-related virus (XMRV) contributes to the pathogenesis of chronic fatigue syndrome (CFS). To investigate the question in a Chinese population, 65 CFS patients and 85 blood donor controls were enrolled and multiplex real-time PCR or reverse transcriptase PCR (RT-PCR) was developed to analyze the XMRV infection status of the study participants. The assay was standardized by constructing plasmid DNAs and armored RNAs as XMRV standards and competitive internal controls (CICs), respectively.

RESULTS: The sensitivities of the multiplex real-time PCR and RT-PCR assays were 20 copies/reaction and 10 IU/ml, respectively, with 100% specificity. The within-run precision coefficient of variation (CV) ranged from 1.76% to 2.80% and 1.70% to 2.59%, while the between-run CV ranged from 1.07% to 2.56% and 1.06% to 2.74%. XMRV was not detected in the 65 CFS patients and 65 normal individuals out of 85 controls.

CONCLUSIONS: This study failed to show XMRV in peripheral blood mononuclear cells (PBMCs) and plasma of Chinese patients with CFS. The absence of XMRV nucleic acids does not support an association between XMRV infection and the development of CFS in Chinese.

 

Source: Hong P, Li J, Li Y. Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome. Virol J. 2010 Sep 13;7:224. doi: 10.1186/1743-422X-7-224. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945957/ (Full article)

 

Mouse retroviruses and chronic fatigue syndrome: Does X (or P) mark the spot?

Five years ago, a retrovirus resembling a murine leukemia virus (MLV) was found in patients with prostate cancer (1), and last year, a similar gammaretrovirus was identified in patients with chronic fatigue syndrome (CFS) (2). The agent was named xenotropic MLV-related virus (XMRV), because its env gene was nearly identical to that of xenotropic MLV, an infectious endogenous MLV that preferentially infects cells from foreign species, including humans (Fig. 1A) (3). The two reports struck a common chord, because the viral sequences found in prostate cancer and CFS were nearly identical. A second common theme emerged in reports from Europe that XMRV was rarely found, if at all, in prostate-cancer samples or patients with CFS; however, other investigators confirmed the presence of XMRV in prostate-cancer samples from North America (4). Although a recent report from the Centers for Disease Control and Prevention (CDC) did not find a link between XMRV and CFS (5), distinct MLV-related sequences are found in serial samples collected from the mid-1990s to 2010 from patients with CFS reported in the study by Lo et al. (6) in PNAS. However, the reasons for the current geographical restriction and the source of the infection are baffling.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936611/

Comment on: Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. [Proc Natl Acad Sci U S A. 2010]

 

Source: Courgnaud V1, Battini JL, Sitbon M, Mason AL. Mouse retroviruses and chronic fatigue syndrome: Does X (or P) mark the spot? Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15666-7. doi: 10.1073/pnas.1007944107. Epub 2010 Aug 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936611/ (Full article)

 

XMRV: does this virus hold the key to myalgic encephalomyelitis/CFS?

Abstract:

In October 2009 a team of researchers from the Whittemore Peterson Institute, in association with the National Cancer Institute and the Cleveland Clinic in the USA, made a discovery that could potentially open the door to useful treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The researchers, led by Judy Mikovits, discovered a significant correlation between ME/CFS and an infectious retrovirus called xenotropic murine leukaemia virus-related virus (XMRV). XMRV is classified as a gammaretrovirus, belonging to the same broad family as HIV, but more closely related to a group of viruses that cause cancers such as leukaemia. XMRV is the first member of the gammaretrovirus genus of retroviruses to be found in humans; the research to fully understand the connection between ME/CFS and XMRV, as well as what it means to have the virus, is ongoing. The disastrous impact of AIDS on human health has significantly raised the profile of retroviruses as human pathogens, and XMRV has potentially serious health implications not only for patients, but also for those caring for people with ME/CFS.

 

Source: Crowhurst G. XMRV: does this virus hold the key to myalgic encephalomyelitis/CFS? Br J Nurs. 2010 Jul 22-Aug 11;19(14):919-22. https://www.ncbi.nlm.nih.gov/pubmed/20647985

 

Absence of evidence of xenotropic murine leukemia virus-related virus infection in persons with chronic fatigue syndrome and healthy controls in the United States

Abstract:

BACKGROUND: XMRV, a xenotropic murine leukemia virus (MuLV)-related virus, was recently identified by PCR testing in 67% of persons with chronic fatigue syndrome (CFS) and in 3.7% of healthy persons from the United States. To investigate the association of XMRV with CFS we tested blood specimens from 51 persons with CFS and 56 healthy persons from the US for evidence of XMRV infection by using serologic and molecular assays. Blinded PCR and serologic testing were performed at the US Centers for Disease Control and Prevention (CDC) and at two additional laboratories.

RESULTS: Archived blood specimens were tested from persons with CFS defined by the 1994 international research case definition and matched healthy controls from Wichita, Kansas and metropolitan, urban, and rural Georgia populations. Serologic testing at CDC utilized a Western blot (WB) assay that showed excellent sensitivity to MuLV and XMRV polyclonal or monoclonal antibodies, and no reactivity on sera from 121 US blood donors or 26 HTLV-and HIV-infected sera. Plasma from 51 CFS cases and plasma from 53 controls were all WB negative. Additional blinded screening of the 51 cases and 53 controls at the Robert Koch Institute using an ELISA employing recombinant Gag and Env XMRV proteins identified weak seroreactivity in one CFS case and a healthy control, which was not confirmed by immunofluorescence. PCR testing at CDC employed a gag and a pol nested PCR assay with a detection threshold of 10 copies in 1 ug of human DNA. DNA specimens from 50 CFS patients and 56 controls and 41 US blood donors were all PCR-negative. Blinded testing by a second nested gag PCR assay at the Blood Systems Research Institute was also negative for DNA specimens from the 50 CFS cases and 56 controls.

CONCLUSIONS: We did not find any evidence of infection with XMRV in our U.S. study population of CFS patients or healthy controls by using multiple molecular and serologic assays. These data do not support an association of XMRV with CFS.

 

Source: Switzer WM, Jia H, Hohn O, Zheng H, Tang S, Shankar A, Bannert N, Simmons G, Hendry RM, Falkenberg VR, Reeves WC, Heneine W. Absence of evidence of xenotropic murine leukemia virus-related virus infection in persons with chronic fatigue syndrome and healthy controls in the United States. Retrovirology. 2010 Jul 1;7:57. doi: 10.1186/1742-4690-7-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908559/ (Full article)

 

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

Abstract:

Lombardi et al. (Reports, 23 October 2009, p. 585) reported an association between the human gammaretrovirus XMRV and chronic fatigue syndrome. However, their results may be misleading because of various potential sources of bias and confounding. If real, the association may lack generalizability because of the specific characteristics of the cases studied and could be due to reverse causality.

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

You can read the rest of this comment here: http://science.sciencemag.org/content/328/5980/825.1.full

 

Source: Sudlow C, Macleod M, Al-Shahi Salman R, Stone J. Comment on “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome”. Science. 2010 May 14;328(5980):825; author reply 825. doi: 10.1126/science.1183545. http://science.sciencemag.org/content/328/5980/825.1.full (Full article)

 

Comment on “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome”

Abstract:

Lombardi et al. (Reports, 23 October 2009, p. 585) reported a significant association between the human retrovirus XMRV and chronic fatigue syndrome (CFS). However, the cases with CFS and the control subjects in their study are poorly described and unlikely to be representative. Independent replication is a critical first step before accepting the validity of this finding.

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

You can read the full comment here: http://science.sciencemag.org/content/328/5980/825.2.full

 

Source: Lloyd A, White P, Wessely S, Sharpe M, Buchwald D. Comment on “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome”. Science. 2010 May 14;328(5980):825; author reply 825. doi: 10.1126/science.1183706. http://science.sciencemag.org/content/328/5980/825.2.full (Full article)

 

Comment on “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome”

Abstract:

Lombardi et al. (Reports, 23 October 2009, p. 585) reported detection of the human gammaretrovirus XMRV in the blood cells of patients with chronic fatigue syndrome (CFS). However, the patient description provided was incomplete. The inclusion of patients from a “CFS outbreak” previously linked with a viral infection, without confirmation in sporadic CFS cases, casts doubt on the role of XMRV in the pathogenesis of CFS.

You can read the full comment here: http://science.sciencemag.org/content/328/5980/825.3.full

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

 

Source: van der Meer JW, Netea MG, Galama JM, van Kuppeveld FJ. Comment on “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome”. Science. 2010 May 14;328(5980):825; author reply 825. doi: 10.1126/science.1183906. http://science.sciencemag.org/content/328/5980/825.3.long (Full article)

 

Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort

Abstract:

OBJECTIVE: The presence of the retrovirus xenotropic murine leukaemia virus-related virus (XMRV) has been reported in peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Considering the potentially great medical and social relevance of such a discovery, we investigated whether this finding could be confirmed in an independent European cohort of patients with chronic fatigue syndrome.

DESIGN: Analysis of a well defined cohort of patients and matched neighbourhood controls by polymerase chain reaction.

SETTING: Certified (ISO 15189) laboratory of clinical virology in a university hospital in the Netherlands. Population Between December 1991 and April 1992, peripheral blood mononuclear cells were isolated from 76 patients and 69 matched neighbourhood controls. In this study we tested cells from 32 patients and 43 controls from whom original cryopreserved phials were still available.

MAIN OUTCOME MEASURES: Detection of XMRV in peripheral blood mononuclear cells by real time polymerase chain reaction assay targeting the XMRV integrase gene and/or a nested polymerase chain reaction assay targeting the XMRV gag gene.

RESULTS: We detected no XMRV sequences in any of the patients or controls in either of the assays, in which relevant positive and negative isolation controls and polymerase chain reaction controls were included. Spiking experiments showed that we were able to detect at least 10 copies of XMRV sequences per 10(5) peripheral blood mononuclear cells by real time as well as by nested polymerase chain reaction, demonstrating high sensitivity of both assays.

CONCLUSIONS: This study failed to show the presence of XMRV in peripheral blood mononuclear cells of patients with chronic fatigue syndrome from a Dutch cohort. These data cast doubt on the claim that XMRV is associated with chronic fatigue syndrome in the majority of patients.

Comment in: Chronic fatigue syndrome and human retrovirus XMRV. [BMJ. 2010]

 

Source: van Kuppeveld FJ, de Jong AS, Lanke KH, Verhaegh GW, Melchers WJ, Swanink CM, Bleijenberg G, Netea MG, Galama JM, van der Meer JW. Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort. BMJ. 2010 Feb 25;340:c1018. doi: 10.1136/bmj.c1018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829122/ (Full article)