Xenotropic murine leukemia virus-related virus
|This article's factual accuracy may be compromised due to out-of-date information. (May 2013)|
|Xenotropic murine leukemia virus-related virus|
|Group:||Group VI (ssRNA-RT)|
|Species:||Xenotropic MuLV-related virus|
Xenotropic murine leukemia virus-related virus (XMRV) is a laboratory-derived gammaretrovirus that arose from the recombination of two endogenous mouse retroviruses during the mid 1990s. The chimeric virus was first described in 2006 as an apparently novel retrovirus and potential human pathogen. Initial reports linked the virus to prostate cancer and later to chronic fatigue syndrome (CFS), leading to considerable interest in the scientific and patient communities, investigation of XMRV as a potential cause of multiple medical conditions, and public health concerns about the safety of the donated blood supply.
XMRV has now been established as a laboratory contaminant. False positive detection of XMRV may also occur because of contamination of clinical specimens and laboratory reagents with other mouse retroviruses or related nucleic acids. Most scientific publications claiming an association of XMRV with CFS or prostate cancer have been retracted, and allegations of research misconduct were leveled against at least one CFS investigator. There is no evidence that XMRV can infect humans, nor has it been demonstrated that XMRV is associated with or causes any human disease.
Classification and genome
XMRV is a murine leukemia virus (MLV) that formed through the recombination of the genomes of two parent MLVs known as preXMRV-1 and preXMRV-2. MLVs belong to the virus family Retroviridae and the genus gammaretrovirus and have a single-stranded RNA genome that replicates through a DNA intermediate. The name XMRV was given because the discoverers of the virus initially thought that it was a novel potential human pathogen that was related to but distinct from MLVs. The XMRV particle is approximately spherical and 80 to 100 nm in diameter.
Several XMRV genomic sequences have been published to date. These sequences are almost identical, an unusual finding as retroviruses replicate their genomes with relatively low fidelity, leading to divergent viral sequences in a single host organism. The results of phylogenetic analyses of XMRV and related murine retroviruses led a group of researchers to conclude that XMRV "might not be a genuine human pathogen".
XMRV was discovered in the laboratories of Joseph DeRisi at the University of California, San Francisco, and Robert Silverman and Eric Klein of the Cleveland Clinic. Silverman had previously cloned and investigated the enzyme ribonuclease L (RNase L), part of the cell’s natural defense against viruses. When activated, RNase L degrades cellular and viral RNA to halt viral replication. In 2002, the "hereditary prostate cancer 1" locus (HPC1) was mapped to the RNase L gene, implicating it in the development of prostate cancer. The cancer-associated "R462Q" mutation results in a glutamine instead of an arginine at position 462 of the RNase L enzyme, reducing its catalytic activity. A man with two copies of this mutation has twice the risk of prostate cancer; one copy raises the risk by 50%. Klein and Silverman hypothesized that "the putative linkage of RNase L alterations to HPC might reflect enhanced susceptibility to a viral agent" and conducted a viral screen of prostate cancer samples, leading to the discovery of XMRV.
Disease association studies
In the initial report on XMRV, the virus was detected in cancerous prostate tissues using a microarray containing samples of genetic material from about 950 viruses. The screen indicated the presence of a gammaretrovirus-like sequence in seven of eleven tumours homozygous for the R462Q mutation, but only in one of five tumours without the mutation. After isolation and cloning of the virus, an expanded screen found it present in 40% of tumours homozygous for R462Q and in only 1.5% of those not. A 2009 study reported evidence of XMRV infection in 23% of subjects independent of the RNase L gene variation, and detection of XMRV was again reported in a 2010 article.
However, numerous studies have failed to find evidence of XMRV in prostate cancer. Researchers in Germany found no XMRV-specific sequences in the DNA or RNA of samples from prostate cancer patients, and no XMRV-specific antibodies were detected in blood serum samples. Another German study found no XMRV association with non-familial (sporadic) prostate cancer, and no XMRV link was found in Irish prostate cancer patients with the R462Q mutation. Similar results were reported in The Netherlands, Japan, and Mexico. Geographical differences were initially suspected as the culprit in these discrepancies, because the positive results were obtained in the United States. However, U.S. studies have also found no evidence of XMRV. Researchers at the National Cancer Institute, Johns Hopkins and the Mayo Clinic tested over 1,000 samples from prostate cancer patients but found no evidence of the virus.
A causal role of XMRV in cancer has not been established, and XMRV does not appear to be capable of transforming cells directly. In prostate cancer, XMRV protein has been found in tumour-associated but nonmalignant stromal cells, but in one study was not found in the actual prostate cancer cells, raising the possibility that the virus may indirectly support tumorigenesis. However, in another study, XMRV proteins and nucleic acids were found in malignant cells.
Chronic fatigue syndrome
In 2009, Lombardi et al. reported finding XMRV DNA in 67% of people with chronic fatigue syndrome (CFS) but in only 4% of healthy controls. The authors reported that patient-derived XMRV could infect cells in vitro and stated that "These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS". The reported association of XMRV and CFS, published in Science, generated worldwide media coverage and subsequent conflicting study results. Independent laboratories from around the world have not detected XMRV in CFS patient groups or control populations, using blood samples or cerebrospinal fluid. Various PCR (Polymerase Chain Reaction) assays and antibody-based detection methods were used in these investigations. Some of the authors of the original CFS report suggested that the widespread failure to replicate their results was attributable to different PCR conditions or to different criteria used to classify patients. However, several negative studies have been conducted with the same PCR primers used in the first investigation. Another study using the original reaction conditions did not detect XMRV in UK patients who "not only had CFS, but had considerable disability". Another study found no XMRV, but did report detection of murine leukemia virus related sequences in the blood of CFS patients. Two reviews have argued that reconciliation of these differences is necessary. The editor-in-chief of the journal Science in June 2011 published an expression of concern, stating that "the validity of the study by Lombardi et al. is now seriously in question". In September 2011, the original authors published a "Partial Retraction" of their 2009 findings, in which they acknowledged that "some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA." A full retraction was issued by Science on December 22, 2011.
An international workshop was convened in September 2010 to aid in resolving the discrepancies. At the meeting, it was announced that Ian Lipkin would oversee a multi-centre trial that would culminate in blinded testing of 150 CFS patients and 150 healthy but comparable donors by laboratories at the Whittemore Peterson Institute, the NIH and the CDC. The results of this trial were made available in mid-2012, and concluded that XMRV was not present in either CFS patients or the control group.
XMRV has been proposed as a cause for conditions including autism, fibromyalgia, multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease. However, there is currently no evidence to support these hypotheses. No XMRV was found in 230 autistic children or in 204 controls, nor was XMRV detected in fibromyalgia or MS patients or in children with idiopathic diseases. In one study, XMRV was detected in a small percentage of patients with weakened immune systems, but other studies found no evidence of XMRV in immunosuppression. Out of more than 500 HIV-1-positive people, none was positive for XMRV, nor was XMRV found in systemic lupus erythematosus patients.
Contamination and artifact
From the first reports of XMRV and disease associations, scientists were concerned that the positive findings could be artifactual, for example as the result of contamination with nucleic acids from mice or mouse viruses. Most proposed retrovirus-disease associations have been prompted by accidental detection of contaminants, and initially promising results were later disproven or failed replication. Virologist Robin Weiss suggested in 2010 that XMRV is likely to be one of these "rumour viruses". The suspicion of contamination grew with an increasing number of negative studies as well as investigations demonstrating contamination.
The results of several studies support the contamination hypothesis. Scientists reported that they found ample sources of contamination in laboratory reagents, tissue samples and blood. Samples that were positive for XMRV were also positive for mouse DNA contaminants. Another article reported on the striking identity of XMRV genomic sequences and their similarity to xenotropic MLVs in several human cell lines. The authors conclude that XMRV contaminated 22Rv1 cell cultures, likely during passage in athymic mice. (Production of laboratory cell lines may involve passaging of tumours in mice.) Identical XMRV integration sites were also found, a phenomenon never before reported for a retrovirus and strongly suggestive of contamination. It has been recommended that studies of XMRV should include more diverse and stringent PCR testing and phylogenetic analysis to detect occurrence of mouse DNA contamination from laboratory sources.
Responding to indications of contamination, the group that reported an association of XMRV with CFS stated that its evidence was not restricted to nucleic acids, but also included antibody-based detection. Their study used murine leukaemia virus antibodies and antigens, not XMRV-specific reagents. Multiple studies have failed to detect XMRV by PCR or antibody-based methods. In one study, several samples that were PCR-negative contained antibodies that interacted with XMRV. However, the authors found that these antibodies were non-specific and also interacted with other viruses. Mayo Clinic researchers also reported on non-specific anti-XMRV antibodies. In another study, only low reactivity with XMRV antigens was found, with no differences between cases and controls. The authors noted that establishing a cutoff for seropositivity was impossible, as no positive sera are available. A study that included samples from the original XMRV-CFS report found no XMRV in patients or controls by PCR, antibody-based methods or viral culture. The authors discovered that some PCR reagents were contaminated with low levels of mouse nucleic acid but pointed out that this could not explain the high XMRV positive rates reported initially.
Blood supply controversy
Transmission of XMRV to or between humans has not been documented. Speculated modes of transmission include sexual and airborne routes, but the mode of human transmission, if any, has not yet been investigated. A study in the Netherlands found no XMRV in the semen of HIV-positive men. Both cell-associated and cell-free transmission have been reported in vitro. XMRV is closely related to several known xenotropic mouse viruses. These viruses recognize and enter cells of non-rodent species by means of the cell-surface xenotropic and polytropic murine leukemia virus receptor (XPR1).
Judy Mikovits of the Whittemore Peterson Institute has stated that XMRV has "almost certainly entered the U.S. blood supply system, but did not know whether it would be susceptible to the same heat treatments that successfully kill off the AIDS virus in blood products." Only fractionated plasma is heat treated, blood for transfusion is not. A United States federal consortium is now working to determine the prevalence of XMRV in the blood supply and the suitability of different detection methods. The preliminary phase of this project yielded inconclusive data. Although four patients tested positive at two of the sites, no patient was positive after repeated testing.
The association of XMRV and CFS reported in Science prompted Health Canada, the New Zealand Blood Service, the Australian Red Cross Blood Service, and the American Red Cross in 2010, to disallow blood donations from individuals with CFS. On June 18, 2010, the American Association of Blood Banks, recommended actively discouraging potential donors who have been diagnosed by a physician as having CFS from donating blood or blood components. As of November 1, 2010, people with CFS are no longer able to donate blood in the UK.
Writing in Cell Host & Microbe, retrovirologists Mark Wainberg and Kuan-Teh Jeang argued that a "scrupulously cautious" risk-benefit analysis is needed to assess the benefits and costs of testing or discarding blood on the basis of XMRV-positive results, taking into account the fact that some individuals and companies could profit from mandatory testing. They drew a parallel with the recent MMR-autism scare, in which conflicts of interest played a role.
- Cingöz, O; Paprotka, T; Delviks-Frankenberry, KA; Wildt, S; Hu, WS; Pathak, VK; Coffin, JM (2012). "Characterization, mapping, and distribution of the two XMRV parental proviruses". Journal of virology 86 (1): 328–38. doi:10.1128/JVI.06022-11. PMC 3255884. PMID 22031947.
- Lee K, Jones KS (February 2010). "The path well traveled: using mammalian retroviruses to guide research on XMRV". Molecular Interventions 10 (1): 20–4. doi:10.1124/mi.10.1.5. PMC 2895355. PMID 20124560.
- Voisin V, Rassart E (May 2007). "Complete genome sequences of the two viral variants of the Graffi MuLV: phylogenetic relationship with other murine leukemia retroviruses". Virology 361 (2): 335–47. doi:10.1016/j.virol.2006.10.045. PMID 17208267.
- Hué, S; Gray, ER; Gall, A; Katzourakis, A; Tan, CP; Houldcroft, CJ; McLaren, S; Pillay, D; et al. (2010). "Disease-associated XMRV sequences are consistent with laboratory contamination". Retrovirology 7 (1): 111. doi:10.1186/1742-4690-7-111. PMC 3018392. PMID 21171979.
- Smith RA (December 2010). "Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses" (PDF). Retrovirology 7 (1): 112. doi:10.1186/1742-4690-7-112. PMC 3022688. PMID 21171980.
- Carpten J, Nupponen N, Isaacs S, et al. (February 2002). "Germline mutations in the ribonuclease L gene in families showing linkage with HPC1". Nature Genetics 30 (2): 181–4. doi:10.1038/ng823. PMID 11799394.
- Silverman RH (2007). "A scientific journey through the 2-5A/RNase L system". Cytokine & Growth Factor Reviews 18 (5–6): 381–8. doi:10.1016/j.cytogfr.2007.06.012. PMC 2075094. PMID 17681844.
- Urisman A, Molinaro RJ, Fischer N, et al. (March 2006). "Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant". PLoS Pathogens 2 (3): e25. doi:10.1371/journal.ppat.0020025. PMC 1434790. PMID 16609730.
- Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR (September 2009). "XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors". Proceedings of the National Academy of Sciences of the United States of America 106 (38): 16351–6. Bibcode:2009PNAS..10616351S. doi:10.1073/pnas.0906922106. PMC 2739868. PMID 19805305.
- Arnold, RS; Makarova, NV; Osunkoya, AO; Suppiah, S; Scott, TA; Johnson, NA; Bhosle, SM; Liotta, D; et al. (2010). "XMRV infection in patients with prostate cancer: novel serologic assay and correlation with PCR and FISH". Urology 75 (4): 755–61. doi:10.1016/j.urology.2010.01.038. PMID 20371060.
- Hohn O, Krause H, Barbarotto P, et al. (2009). "Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients". Retrovirology 6: 92. doi:10.1186/1742-4690-6-92. PMC 2770519. PMID 19835577.
- Fischer N, Hellwinkel O, Schulz C, et al. (November 2008). "Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer". Journal of Clinical Virology 43 (3): 277–83. doi:10.1016/j.jcv.2008.04.016. PMID 18823818.
- D'Arcy F, Foley R, Perry A, et al. (March 2008). "No evidence of XMRV in Irish prostate cancer patients with the R462Q mutation". European Urology Supplements 7 (3): 271. doi:10.1016/S1569-9056(08)60798-8.
- Verhaegh, GW; De Jong, AS; Smit, FP; Jannink, SA; Melchers, WJ; Schalken, JA (2011). "Prevalence of human xenotropic murine leukemia virus-related gammaretrovirus (XMRV) in Dutch prostate cancer patients". The Prostate 71 (4): 415–20. doi:10.1002/pros.21255. PMID 20878949.
- Furuta, RA; Miyazawa, T; Sugiyama, T; Kuratsune, H; Ikeda, Y; Sato, E; Misawa, N; Nakatomi, Y; et al. (2011). "No association of xenotropic murine leukemia virus-related virus with prostate cancer or chronic fatigue syndrome in Japan". Retrovirology 8: 20. doi:10.1186/1742-4690-8-20. PMC 3065418. PMID 21414229.
- Martinez-Fierro, ML; Leach, RJ; Gomez-Guerra, LS; Garza-Guajardo, R; Johnson-Pais, T; Beuten, J; Morales-Rodriguez, IB; Hernandez-Ordoñez, MA; et al. (2010). "Identification of viral infections in the prostate and evaluation of their association with cancer". BMC cancer 10: 326. doi:10.1186/1471-2407-10-326. PMC 2912861. PMID 20576103.
- Menéndez-Arias, L (2011). "Evidence and controversies on the role of XMRV in prostate cancer and chronic fatigue syndrome". Reviews in medical virology 21 (1): 3–17. doi:10.1002/rmv.673. PMID 21294212.
- Aloia, AL; Sfanos, KS; Isaacs, WB; Zheng, Q; Maldarelli, F; De Marzo, AM; Rein, A (2010). "XMRV: a new virus in prostate cancer?". Cancer Research 70 (24): 10028–33. doi:10.1158/0008-5472.CAN-10-2837. PMC 3005136. PMID 20966126.
- Sfanos, KS; Sauvageot, J; Fedor, HL; Dick, JD; De Marzo, AM; Isaacs, WB (2008). "A molecular analysis of prokaryotic and viral DNA sequences in prostate tissue from patients with prostate cancer indicates the presence of multiple and diverse microorganisms". The Prostate 68 (3): 306–20. doi:10.1002/pros.20680. PMID 18163428.
- Sakuma, T; Hue, S; Squillace, KA; Tonne, JM; Blackburn, PR; Ohmine, S; Thatava, T; Towers, GJ; Ikeda, Y (2011). "No Evidence of XMRV in Prostate Cancer Cohorts in the Midwestern United States". Retrovirology 8 (1): 23. doi:10.1186/1742-4690-8-23. PMC 3077333. PMID 21447170.
- Metzger MJ, Holguin CJ, Mendoza R, Miller AD (February 2010). "The prostate cancer-associated human retrovirus XMRV lacks direct transforming activity but can induce low rates of transformation in cultured cells". Journal of Virology 84 (4): 1874–80. doi:10.1128/JVI.01941-09. PMC 2812358. PMID 20007266.
- McLaughlin-Drubin ME, Munger K (March 2008). "Viruses associated with human cancer". Biochimica et Biophysica Acta 1782 (3): 127–50. doi:10.1016/j.bbadis.2007.12.005. PMC 2267909. PMID 18201576.
- Lombardi VC, Ruscetti FW, Das Gupta J, et al. (October 2009). "Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome". Science 326 (5952): 585–9. Bibcode:2009Sci...326..585L. doi:10.1126/science.1179052. PMID 19815723. (Retracted)
- Erlwein O, Kaye S, McClure MO, et al. (2010). Nixon DF, ed. "Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome". PLoS ONE 5 (1): e8519. Bibcode:2010PLoSO...5.8519E. doi:10.1371/journal.pone.0008519. PMC 2795199. PMID 20066031.
- Groom, Harriet C T; Boucherit, Virginie C; Makinson, Kerry; Randal, Edward; Baptista, Sarah; Hagan, Suzanne; Gow, John W; Mattes, Frank M; et al. (2010). "Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome". Retrovirology 7: 10. doi:10.1186/1742-4690-7-10. PMC 2839973. PMID 20156349.
- van Kuppeveld FJ, Jong AS, Lanke KH, et al. (2010). "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 340: c1018. doi:10.1136/bmj.c1018. PMC 2829122. PMID 20185493.
- Switzer, William M; Jia, Hongwei; Hohn, Oliver; Zheng, Haoqiang; Tang, Shaohua; Shankar, Anupama; Bannert, Norbert; Simmons, Graham; et al. (2010). "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 7: 57. doi:10.1186/1742-4690-7-57. PMC 2908559. PMID 20594299.
- Henrich, TJ; Li, JZ; Felsenstein, D; Kotton, CN; Plenge, RM; Pereyra, F; Marty, FM; Lin, NH; et al. (2010). "Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions". The Journal of infectious diseases 202 (10): 1478–81. doi:10.1086/657168. PMC 2957553. PMID 20936980.
- Hong, P; Li, J; Li, Y (2010). "Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome". Virology Journal 7: 224. doi:10.1186/1743-422X-7-224. PMC 2945957. PMID 20836869.
- Hohn, Oliver; Strohschein, Kristin; Brandt, Alexander U.; Seeher, Sandra; Klein, Sandra; Kurth, Reinhard; Paul, Friedemann; Meisel, Christian; et al. (2010). Digard, Paul, ed. "No Evidence for XMRV in German CFS and MS Patients with Fatigue Despite the Ability of the Virus to Infect Human Blood Cells In Vitro". PLoS ONE 5 (12): e15632. Bibcode:2010PLoSO...515632H. doi:10.1371/journal.pone.0015632. PMC 3008728. PMID 21203514.
- Satterfield, B. C.; Garcia, R. A.; Jia, H.; Tang, S.; Zheng, H.; Switzer, W. M. (2011). "Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses". Retrovirology 8: 12. doi:10.1186/1742-4690-8-12. PMC 3050813. PMID 21342521.
- Erlwein, O; Robinson, MJ; Kaye, S; Wills, G; Izui, S; Wessely, S; Weber, J; Cleare, A; et al. (2011). Hasenkrug, Kim, ed. "Investigation into the Presence of and Serological Response to XMRV in CFS Patients". PLoS ONE 6 (3): e17592. Bibcode:2011PLoSO...617592E. doi:10.1371/journal.pone.0017592. PMC 3052320. PMID 21408077.
- Furuta, RA; Miyazawa, T; Sugiyama, T; Kuratsune, H; Ikeda, Y; Sato, E; Misawa, N; Nakatomi, Y; et al. (2011). "No association of xenotropic murine leukemia virus-related virus with prostate cancer or chronic fatigue syndrome in Japan". Retrovirology 8: 20. doi:10.1186/1742-4690-8-20. PMC 3065418. PMID 21414229.
- Schutzer, Steven E.; Rounds, Megan A.; Natelson, Benjamin H.; Ecker, David J.; Eshoo, Mark W. (2011). "Analysis of cerebrospinal fluid from chronic fatigue patients for multiple human ubiquitous viruses and XMRV". Annals of Neurology 69 (4): n/a–n/a. doi:10.1002/ana.22389. PMID 21472770.
- Mikovits, J. A.; Ruscetti, F. W. (2010). "Response to Comments on "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome"". Science 328 (5980): 825–825. Bibcode:2010Sci...328..825M. doi:10.1126/science.1184548.
- Lo SC, Pripuzova N, Li B, Komaroff AL, Hung GC, Wang R, Alter HJ (September 7, 2010). "Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors". Proceedings of the National Academy of Sciences of the United States of America 107 (36): 15874–15879. Bibcode:2010PNAS..10715874L. doi:10.1073/pnas.1006901107. PMC 2936598. PMID 20798047. (Retracted)
- Baraniuk, James N (April 7, 2010). "Xenotropic Murine Leukemia Virus-Related Virus in Chronic Fatigue Syndrome and Prostate Cancer". Current Allergy and Asthma Reports (Current Medicine Group LLC) 10 (3): 210–4. doi:10.1007/s11882-010-0106-2. ISSN 1529-7322. PMC 2880572. PMID 20425007. Retrieved 2010-04-25.
- Silverman, R. "The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome", Nature Reviews Urology, June 1, 2010.
- Alberts, B. (2011). "Editorial Expression of Concern". Science 333: 35. Bibcode:2011Sci...333...35A. doi:10.1126/science.1208542. PMID 21628391.
- Silverman, R. (2011). "Partial Retraction". Science 334: 176. Bibcode:2011Sci...334..176S. doi:10.1126/science.1212182. PMID 21940859.
- Cohen, Jon (22 December 2011). "In a Rare Move, Science Without Authors' Consent Retracts Paper That Tied Mouse Virus to Chronic Fatigue Syndrome". Retrieved 22 December 2011.
- Stoye, JP; Silverman, RH; Boucher, CA; Le Grice, SF (2010). "The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop". Retrovirology 7: 113. doi:10.1186/1742-4690-7-113. PMC 3022689. PMID 21176195.
- Callaway, Ewen (March 14, 2011). "Virology: Fighting for a cause". Nature 471 (7338): 282–85. Bibcode:2011Natur.471..282C. doi:10.1038/471282a.
- Tsouderos, Trine (17 March 2011). "Research casts doubt on theory of cause of chronic fatigue". Chicago Tribune.
- Whittemore Peterson Institute claims.
- Satterfield BC, Garcia RA, Gurrieri F, Schwartz CE (2010). "PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV) and autism". Mol Autism 1 (1): 14. doi:10.1186/2040-2392-1-14. PMC 2964727. PMID 20946639.
- Luczkowiak, J; Sierra, O; González-Martín, JJ; Herrero-Beaumont, G; Delgado, R (2011). "No xenotropic murine leukemia virus-related virus detected in fibromyalgia patients". Emerging Infectious Diseases 17 (2): 314–5. doi:10.3201/eid1702.100978. PMC 3204766. PMID 21291619.
- Maric, R; Pedersen, FS; Kjeldbjerg, A; Moeller-Larsen, A; Bahrami, S; Brudek, T; Petersen, T; Christensen, T (2010). "Absence of xenotropic murine leukaemia virus-related virus in Danish patients with multiple sclerosis". Journal of Clinical Virology 49 (3): 227–8. doi:10.1016/j.jcv.2010.08.003. PMID 20829105.
- Jeziorski, E; Foulongne, V; Ludwig, C; Louhaem, D; Chiocchia, G; Segondy, M; Rodière, M; Sitbon, M; Courgnaud, V (2010). "No evidence for XMRV association in pediatric idiopathic diseases in France". Retrovirology 7: 63. doi:10.1186/1742-4690-7-63. PMC 2920251. PMID 20678193.
- Fischer N, Schulz C, Stieler K, Hohn O, Lange C, Drosten C, Aepfelbacher M (June 2010). "Xenotropic murine leukemia virus-related gammaretrovirus in respiratory tract". Emerg Infect Dis 16 (6): 1000–2. doi:10.3201/eid1606.100066. PMC 3086240. PMID 20507757. PDF: http://www.cdc.gov/eid/content/16/6/pdfs/1000.pdf
- Barnes, E; Flanagan, P; Brown, A; Robinson, N; Brown, H; McClure, M; Oxenius, A; Collier, J; et al. (2010). "Failure to detect xenotropic murine leukemia virus-related virus in blood of individuals at high risk of blood-borne viral infections". The Journal of infectious diseases 202 (10): 1482–5. doi:10.1086/657167. PMID 20936982.
- Gray, Eleanor R.; Garson, Jeremy A.; Breuer, Judith; Edwards, Simon; Kellam, Paul; Pillay, Deenan; Towers, Greg J. (2011). Rossi, John, ed. "No Evidence of XMRV or Related Retroviruses in a London HIV-1-Positive Patient Cohort". PLoS ONE 6 (3): e18096. Bibcode:2011PLoSO...6E8096G. doi:10.1371/journal.pone.0018096. PMC 3063244. PMID 21448291.
- Balada, E.; Castro-Marrero, J.; Felip, L.; Vilardell-Tarrés, M.; Ordi-Ros, J. (2011). "Xenotropic Murine Leukemia Virus-Related Virus (XMRV) in Patients with Systemic Lupus Erythematosus". Journal of Clinical Immunology 31 (4): 584–7. doi:10.1007/s10875-011-9535-5. PMID 21509625.
- Robinson, MJ; Erlwein, OW; Kaye, S; Weber, J; Cingoz, O; Patel, A; Walker, MM; Kim, WJ; et al. (2010). "Mouse DNA contamination in human tissue tested for XMRV". Retrovirology 7: 108. doi:10.1186/1742-4690-7-108. PMC 3019155. PMID 21171966.
- Weiss, RA (2010). "A cautionary tale of virus and disease". BMC biology 8: 124. doi:10.1186/1741-7007-8-124. PMC 2946284. PMID 20920148.
- Garson, JA; Kellam, P; Towers, GJ (2011). "Analysis of XMRV integration sites from human prostate cancer tissues suggests PCR contamination rather than genuine human infection". Retrovirology 8: 13. doi:10.1186/1742-4690-8-13. PMC 3050814. PMID 21352548.
- Shan, H (2011). "What is XMRV and should we be worried about it?". Transfusion 51 (3): 450–3. doi:10.1111/j.1537-2995.2011.03070.x. PMID 21388387.
- Kaiser, J (2011). "Chronic fatigue syndrome. Studies point to possible contamination in XMRV findings". Science 331 (6013): 17. Bibcode:2011Sci...331...17K. doi:10.1126/science.331.6013.17. PMID 21212329.
- Cohen, J. (2011). "More Negative Data for Link Between Mouse Virus and Human Disease". Science 331 (6022): 1253–1254. doi:10.1126/science.331.6022.1253. PMID 21393520.
- Carlowe, J (2010). "Chronic fatigue syndrome is not caused by XMRV virus, study shows". BMJ (Clinical research ed.) 341: c7358. doi:10.1136/bmj.c7358. PMID 21177733.
- Shin, C. H.; Bateman, L.; Schlaberg, R.; Bunker, A. M.; Leonard, C. J.; Hughen, R. W.; Light, A. R.; Light, K. C.; Singh, I. R. (2011). "Absence of XMRV and other MLV-related viruses in patients with Chronic Fatigue Syndrome". Journal of Virology 85 (14): 7195–7202. doi:10.1128/JVI.00693-11. PMC 3126563. PMID 21543496.
- Sato, E; Furuta, RA; Miyazawa, T (2010). "An endogenous murine leukemia viral genome contaminant in a commercial RT-PCR kit is amplified using standard primers for XMRV". Retrovirology 7: 110. doi:10.1186/1742-4690-7-110. PMC 3024226. PMID 21171978.
- Oakes, B; Tai, AK; Cingöz, O; Henefield, MH; Levine, S; Coffin, JM; Huber, BT (2010). "Contamination of human DNA samples with mouse DNA can lead to false detection of XMRV-like sequences". Retrovirology 7: 109. doi:10.1186/1742-4690-7-109. PMC 3022687. PMID 21171973.
- Kaiser, Jocelyn (7 January 2011). "Studies Point to Possible Contamination in XMRV Findings". Science 331 (6013): 17. Bibcode:2011Sci...331...17K. doi:10.1126/science.331.6013.17. PMID 21212329.
- Sabunciyan, S; Mandelberg, N; Rabkin, CS; Yolken, R; Viscidi, R (2011). "No difference in antibody titers against xenotropic MLV related virus in prostate cancer cases and cancer-free controls". Molecular and Cellular Probes 25 (2-3): 134–6. doi:10.1016/j.mcp.2011.01.005. PMID 21281710.
- Hong S, Klein EA, Das Gupta J, et al. (July 2009). "Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer". Journal of Virology 83 (14): 6995–7003. doi:10.1128/JVI.00268-09. PMC 2704761. PMID 19403677.
- Brower V (May 2009). "Is a retrovirus implicated in familial prostate cancer?". Journal of the National Cancer Institute 101 (10): 700–1. doi:10.1093/jnci/djp137. PMID 19436028.
- Eastman, Peggy (January 2009). "Prostate Cancer: New Data Help Refine Risk Stratification". Oncology Times 31 (2): 32–3. doi:10.1097/01.COT.0000345494.12042.f8.
- Cornelissen, M; Zorgdrager, F; Blom, P; Jurriaans, S; Repping, S; Van Leeuwen, E; Bakker, M; Berkhout, B; Van Der Kuyl, AC (2010). Nixon, Douglas F., ed. "Lack of detection of XMRV in seminal plasma from HIV-1 infected men in The Netherlands". PLoS ONE 5 (8): e12040. Bibcode:2010PLoSO...512040C. doi:10.1371/journal.pone.0012040. PMC 2919391. PMID 20706581.
- Kozak, CA (2010). "The mouse "xenotropic" gammaretroviruses and their XPR1 receptor". Retrovirology 7: 101. doi:10.1186/1742-4690-7-101. PMC 3009702. PMID 21118532.
- Virus leads Canadian Blood Services to ban certain donors Joseph Hall, The Hamilton Spectator, 06 April 2010.
- Klein HG, Dodd RY, Hollinger FB, Katz LM, Kleinman S, McCleary KK, Silverman RH, Stramer SL; AABB Interorganizational Task Force on XMRV (2011). "Xenotropic murine leukemia virus-related virus (XMRV) and blood transfusion: report of the AABB interorganizational XMRV task force". Transfusion. 51 (3): 654–61. doi:10.1111/j.1537-2995.2010.03012.x. PMID 21235597.
- National Center for Preparedness, Detection, and Control of Infectious Diseases (NCPDCID). "Xenotropic Murine Leukemia Virus-related Virus (XMRV)". Retrieved 2010-02-21.
- "Potential Risk to Blood Supply Probed". The Wall Street Journal. 2010-04-04.
- "Blood Products Advisory Committee Meeting Transcript". FDA.org. 2010-12-14. Retrieved 2011-05-24.
- "No blood from chronic fatigue donors: agency - Health - CBC News". 2010-04-07. Retrieved 2011-03-23.
- Canadian Blood Services Responds to Possible New Blood Safety Threat
- Atkinson, K (2010-04-21). "Chronic Fatigue Set To Disqualify Blood Donors". Voxy.co.nz. Retrieved 2010-06-25.
- Blood Service updates CFS donor policy
- Cortez, Michelle (2010-12-04). "Red Cross Bans Chronic Fatigue Patients From Donating Blood". Bloomberg. Retrieved 2011-01-21.
- "Recommendation on Chronic Fatigue Syndrome and Blood Donation". Aabb.org. 2010-06-18. Retrieved 2011-01-21.
- Roberts, Michelle (2010-10-07). "BBC News - ME patients face UK ban on donating blood". Bbc.co.uk. Retrieved 2011-01-21.
- Wainberg, M. A.; Jeang, K. T. (2011). "XMRV as a Human Pathogen?". Cell Host & Microbe 9 (4): 260–262. doi:10.1016/j.chom.2011.04.001. PMID 21501825.
- XMRV Fact Sheet, AABB.org (formerly American Association of Blood Banks), Updated June 18, 2010
- Center for Disease Control: XMRV Information
- Nature: Crystal structure of XMRV protease differs from the structures of other retropepsins