Xenotropic murine leukemia virus-related virus

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" Xenotropic MLV-related virus "
Xmrv.gif

XMRV virions, EM

Systematics
Classification : Viruses
Family : Retroviridae
Subfamily : Orthoretrovirinae
Genre : Gamma retroviruses
Type : "Xenotropic MLV-related virus"
Taxonomic characteristics
Genome : (+) ssRNA -RT linear
Baltimore : Group 6
Cover : available
Scientific name
"Xenotropic MLV-related virus"
Short name
"XMRV"
Left
NCBI  Reference: NC_007815.1
ICTVdB Virus Code : 00.061.1.02

" Xenotropic murine leukemia virus-related virus " ( scientifically " Xenotropic MLV-related virus ", " Xenotropic MuLV-related virus ", " XMRV ") is a proposed virus species in the genus Gammaretrovirus , which first appeared in 2006 as an apparently novel human pathogen in tissue samples from men with prostate cancer . Initial reports had the virus falsely with prostate cancer and later with the chronic fatigue syndrome ( English Chronic fatigue syndrome brought CFS) in conjunction. Subsequent investigations showed that XMRV was indeed a laboratory contamination and not a novel pathogen.

history

"XMRV" was discovered in a laboratory at the University of California, San Francisco under Joseph de Risi, and Robert Silverman and Eric Klein (Cleveland Clinic). Silverman suggested that the putative association of RNase L variations and increased cancer risk may reflect increased susceptibility to a causative virus. This led to the discovery of "XMRV". It is now known that "XMRV" is a virus that does not occur naturally, as the XMRV sequence could only be detected by a few working groups, with only very small differences in the genome sequence - unique in the case of RNA and retroviruses occurred. Furthermore, there was no dose-effect relationship and no evidence of virions (e.g. by TEM or MALDI-TOF ) or of immune reactions (e.g. by ELISA , ELISPOT or Western Blot ) was provided. Finally, the underlying test results could not be repeated several times by other working groups (see reproducibility ). Therefore, publications regarding the pathogenesis of chronic fatigue syndrome have already been withdrawn by the publisher (see section Discussion of diseases ).

Classification and genome

"XMRV" belongs to the family of retroviruses and to the genus of gamma retroviruses . It has a double-stranded RNA genome and is reproduced from a DNA copy. Its name refers to the close relationship to the murine leukemia virus . The genome, with an estimated length of 8100 nucleotides, is 93-94% identical to some exogenous mouse viruses.

Some XMRV gene sequences have already been published. These sequences are almost identical, which is unusual because retroviruses replicate their genome with relative inaccuracy; this normally leads to high mutation rates - as in the example of HIV .

transmission

"XMRV" is closely related to some known xenotropic mouse viruses. These viruses recognize and infect cells from non-rodents using the XPR1 receptor (xenotropic and polytropic murine leukemia virus receptor). Some authors speculate that the virus may be sexually transmitted, but human-to-human transmission, if any, has not been studied. Both cellular and cell-free transmission could be observed in vitro .

pharmacology

A 2010 study published in the Public Library of Science concluded that four AIDS drugs could also suppress the replication of "XMRV". These were two retroviral integrase inhibitors ( raltegravir , L-000870812), and two nucleoside reverse transcriptase inhibitors ( tenofovir and zidovudine ). Also have synergistic effects observed these drugs in common use.

Discussion about diseases

Relationships between XMRV-positive samples and prostate cancer in patients with a mutation of RNase L (R462Q) or chronic fatigue syndrome have been established , which have since proven to be findings due to laboratory contamination . Two studies linked the virus to prostate cancer, while other studies found no link.

The original observations have also been refuted by several studies with regard to the possible connection to chronic fatigue syndrome (CFS).

Because of the association between XMRV and CFS, as reported in Science , the Canadian Department of Health, New Zealand Blood Banks, and the Australian Red Cross temporarily banned people with CFS from donating blood. On June 18, 2010, the American AABB also recommended provisionally not to accept blood donations from CFS patients.

Since only extremely sensitive detection methods were used to detect the retrovirus ( PCR or nested PCR), the suspicion has been expressed that the detection could be based on laboratory contamination. Several studies support this view, as they have demonstrated the contamination of commercial kits with mouse (murine) DNA, and the DNA sequences found could in part be traced back to the prostate carcinoma cell line 22Rv1 used in many laboratories.

In September 2011, the authors of the original study, which allegedly linked “XMRV” and CFS, withdrew substantial parts of their publication. In December 2011, all publication by Science magazine was revoked.

Web links

Individual evidence

  1. ↑ XMRV (Xenotropic Murine Leukemia Virus-related Virus) | CDC ( en-us )
  2. ↑ A. Urisman, RJ Molinaro, N. Fischer, SJ Plummer, G. Casey, EAKlein, K. Malathi, C. Magi-Galluzzi, RR Tubbs, D. Ganem: Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant . In: PLoS Pathog . 2, No. 3, 2006, p. E25. doi : 10.1371 / journal.ppat.0020025 . PMID 16609730 . PMC 1434790 (free full text). (Moved in, see doi: 10.1371 / annotation / 7e2efc01-2e9b-4e9b-aef0-87ab0e4e4732 )
  3. ↑ NCI's Vinay K. Pathak on the "De-Discovery" of a Retrovirus-Disease Link , Science Watch , Fast Breaking Papers, 2012, November 16, 2015
  4. ↑ Tobias Paprotka, Krista A. Delviks-Frankenberry, Oya Cingöz, Anthony Martinez, Kung Hsing-Jien, Clifford G. Tepper, Hu Wei-Shau, Matthew J. Fivash Jr., John M. Coffin, Vinay K. Pathak: Recombinant origin of the retrovirus XMRV . In: Science . 333, No. 6038, July 1, 2011, ISSN  0036-8075 , pp. 97-101. bibcode : 2011Sci ... 333 ... 97P . doi : 10.1126 / science.1205292 . PMID 21628392 . PMC 3278917 (free full text). via EBSCO login
  5. ↑ J. Carpten, N. Nupponen, S. Isaacs et al : Germline mutations in the ribonuclease L gene in families showing linkage with HPC1 . In: Nature Genetics . tape 30 , no. 2 , February 2002, p. 181-184 , doi : 10.1038 / ng823 , PMID 11799394 .
  6. ↑ A. Urisman, RJ Molinaro, N. Fischer, SJ Plummer, G. Casey, EA Klein, K. Malathi, C. Magi-Galluzzi, RR Tubbs, D. Ganem, RH Silverman, JL DeRisi: Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. In: PLoS Pathog . 2 (3), 2006, Art. No. e25. PMID 16609730 .
  7. ↑ a b c K. Lee, KS Jones: The path well traveled: using mammalian retroviruses to guide research on XMRV . In: Molecular Interventions . tape 10 , no. 1 , February 2010, p. 20–24 , doi : 10.1124 / mi.10.1.5 , PMID 20124560 , PMC 2895355 (free full text).
  8. ↑ V. Voisin, E. Rassart: Complete genome sequences of the two viral variants of the Graffi MuLV: phylogenetic relationship with other murine leukemia retroviruses . In: Virology . tape 361 , no. 2 , May 2007, p. 335-347 , doi : 10.1016 / j.virol.2006.10.045 , PMID 17208267 .
  9. ↑ S. Hong, EA Klein, J. Das Gupta et al: Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer . In: Journal of Virology . tape 83 , no. July 14 , 2009, p. 6995-7003 , doi : 10.1128 / JVI.00268-09 , PMID 19403677 , PMC 2704761 (free full text).
  10. ^ V. Brower: Is a retrovirus implicated in familial prostate cancer? In: Journal of the National Cancer Institute . tape 101 , no. May 10 , 2009, pp. 700-701 , doi : 10.1093 / jnci / djp137 , PMID 19436028 .
  11. ^ Peggy Eastman: Prostate Cancer: New Data Help Refine Risk Stratification . In: Oncology Times . tape 31 , no. 2 , January 2009, p. 32-33 , doi : 10.1097 / 01.COT.0000345494.12042.f8 ( lww.com ).
  12. ↑ a b V. C. Lombardi, FW Ruscetti, J. Das Gupta et al. : Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome . In: Science . tape 326 , no. 5952 , October 2009, p. 585-589 , doi : 10.1126 / science.1179052 , PMID 19815723 .
  13. ↑ Ila R. Singh, John E. Gorzynski, Daria Drobysheva, Leda Bassit, Raymond F. Schinazi: Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome . In: PLOS ONE . tape 5 , no. 4 , p. e9948 , doi : 10.1371 / journal.pone.0009948 .
  14. ^ RH Silverman: A scientific journey through the 2-5A / RNase L system . In: Cytokine & Growth Factor Reviews . tape 18 , no. 5-6 , 2007, pp. 381-388 , doi : 10.1016 / j.cytogfr.2007.06.012 , PMID 17681844 , PMC 2075094 (free full text).
  15. ^ R. Schlaberg, DJ Choe, KR Brown, HM Thaker, IR Singh: XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors . In: Proceedings of the National Academy of Sciences of the United States of America . tape 106 , no. 38 , September 2009, p. 16351-16356 , doi : 10.1073 / pnas.0906922106 , PMID 19805305 , PMC 2739868 (free full text).
  16. ↑ O. Hohn, K. Strohschein, AU Brandt, S. Seeher, S. Klein, R. Kurth, F. Paul, C. Meisel, C. Scheibenbogen, N. Bannert: 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. In: PloS one. Volume 5, Number 12, 2010, Art. No. e15632, ISSN  1932-6203 . doi: 10.1371 / journal.pone.0015632 . PMID 21203514 . PMC 3008728 (free full text).
  17. ↑ O. Hohn, H. Krause, P. Barbarotto u. a .: Lack of evidence for xenotropic murine leukemia virus-related virus (XMRV) in German prostate cancer patients . In: Retrovirology . tape 6 , 2009, p. 92 , doi : 10.1186 / 1742-4690-6-92 , PMID 19835577 , PMC 2770519 (free full text).
  18. ↑ N. Fischer, O. Hellwinkel, C. Schulz et al: Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer . In: Journal of Clinical Virology . tape 43 , no. 3 , November 2008, p. 277-283 , doi : 10.1016 / j.jcv.2008.04.016 , PMID 18823818 .
  19. ↑ F. D'Arcy, R. Foley, A. Perry et al .: No evidence of XMRV in Irish prostate cancer patients with the R462Q mutation . In: European Urology Supplements . tape 7 , March 2008, p. 271 , doi : 10.1016 / S1569-9056 (08) 60798-8 .
  20. ↑ MJ Metzger, CJ Holguin, R. Mendoza, AD Miller: The prostate cancer-associated human retrovirus XMRV lacks direct transforming activity but can induce low rates of transformation in cultured cells . In: Journal of Virology . tape 84 , no. 4 , February 2010, p. 1874-1880 , doi : 10.1128 / JVI.01941-09 , PMID 20007266 , PMC 2812358 (free full text).
  21. ↑ ME McLaughlin-Drubin, K. Munger: Viruses associated with human cancer . In: Biochimica et Biophysica Acta . tape 1782 , no. 3 , March 2008, p. 127–150 , doi : 10.1016 / j.bbadis.2007.12.005 , PMID 18201576 , PMC 2267909 (free full text).
  22. ↑ KS Sfanos, AL Aloia, AM De Marzo, A. Rein: XMRV and prostate cancer-a 'final' perspective. In: Nature Reviews Urology . 9 (2), 2012, pp. 111-118. doi: 10.1038 / nrurol.2011.225 . PMID 22231291 .
  23. ↑ Harriet CT Groom, Virginie C Boucherit, Kerry Makinson, Edward Randal, Sarah Baptista, Suzanne Hagan, John W Gow, Frank M Mattes: Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome . In: Retrovirology . tape 7 , 2010, p. 10 , doi : 10.1186 / 1742-4690-7-10 , PMID 20156349 , PMC 2839973 (free full text).
  24. ↑ FJ van Kuppeveld, AS Jong, KH Lanke et al. : 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 . In: BMJ . tape 340 , 2010, p. c1018 , doi : 10.1136 / bmj.c1018 , PMID 20185493 , PMC 2829122 (free full text) - ( bmj.com ).
  25. ↑ William Switzer, Hongwei Jia, Oliver Hohn, HaoQiang Zheng, Shaohua Tang, Anupama Shankar, Norbert Bannert, Graham Simmons, R Michael Hendry, Virginia Falkenberg, William Reeves, Walid Heneine: Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the United States . In: Retrovirology . tape 7 , no. 1 , 2010, p. 57 , doi : 10.1186 / 1742-4690-7-57 .
  26. ↑ O. Erlwein, S. Kaye, MO McClure et al. : Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome . In: PLoS ONE . tape 5 , no. 1 , 2010, p. e8519 , doi : 10.1371 / journal.pone.0008519 , PMID 20066031 , PMC 2795199 (free full text).
  27. ↑ MS Karafin, SL Stramer: The scientific method at work: xenotropic murine leukemia virus-related virus is neither a cause of chronic fatigue syndrome nor a threat to the blood supply. In: transfusion . 52 (2), 2012, pp. 222-225. doi: 10.1111 / j.1537-2995.2011.03518.x . PMID 22239209 .
  28. ↑ cbcnews: No blood from chronic fatigue donors: agency. ( Memento from May 26, 2012 in the web archive archive.today ) April 7, 2010.
  29. ↑ Canadian Blood Services Responds to Possible New Blood Safety Threat. ( Memento from April 26, 2013 in the web archive archive.today )
  30. ↑ K. Atkinson: Chronic Fatigue Set To Disqualify Blood Donors. Voxy.co.nz, April 21, 2010, accessed June 25, 2010 .
  31. ^ Australian Red Cross (Blood Service): Blood Service updates CFS donor policy. ( Memento of October 14, 2013 in the Internet Archive ) April 23, 2010.
  32. ^ Advancing Transfusion and Cellular Therapies Worldwide: Recommendation on Chronic Fatigue Syndrome and Blood Donation. ( Memento from February 21, 2014 in the web archive archive.today ) June 18, 2010.
  33. ^ RA Smith: Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses. In: Retrovirology. 7, 2010, p. 112. (full text)
  34. ↑ S. Hue, ER Gray, A. Gall, A. Katzourakis, CP Tan, CJ Houldcroft, S. McLaren, D. Pillay, A. Futreal, JA Garson, OG Pybus, P. Kellam, GJ Towers: Disease-associated XMRV sequences are consistent with laboratory contamination. In: Retrovirology. 7 (1), 2010, p. 111. (full text)
  35. ↑ E. Sato, RA Furuta, T. Miyazawa: An endogenous murine leukemia viral genome contaminant in a commercial RT-PCR Kit is amplified using standard primers for XMRV. In: Retrovirology. 7, 2010, p. 110. (full text)
  36. ↑ MJ Robinson, OW Erlwein, S. Kaye, J. Weber, O. Cingoz, A. Patel, MM Walker, WJ Kim, M. Uiprasertkul, JM Coffin, MO McClure: Mouse DNA contamination in human tissue tested for XMRV. In: Retrovirology. Volume 7, 2010, p. 108, ISSN  1742-4690 . doi: 10.1186 / 1742-4690-7-108 . PMID 21171966 . PMC 301915 (free full text).
  37. ↑ B. Oakes, AK Tai, O. Cingöz, MH Henefield, S. Levine, JM Coffin, BT Huber: Contamination of human DNA samples with mouse DNA can lead to false detection of XMRV-like sequences. In: Retrovirology. Volume 7, 2010, p. 109, ISSN  1742-4690 . doi: 10.1186 / 1742-4690-7-109 . PMID 21171973 . PMC 302268 (free full text).
  38. ↑ Robert H. Silverman, Jaydip Das Gupta, Vincent C. Lombardi, Francis W. Ruscetti et al. : Partial retraction. In: Science Express. (ePub ahead of print), http://www.sciencemag.org/content/early/2011/09/21/science.1212182
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  40. ↑ Reason for withdrawing the article . Retrieved February 18, 2012.