http://en.wikisage.org/w/index.php?title=Xenotropic_murine_leukemia_virus-related_virus&feed=atom&action=historyXenotropic murine leukemia virus-related virus - Revision history2024-03-29T15:32:50ZRevision history for this page on the wikiMediaWiki 1.41.0http://en.wikisage.org/w/index.php?title=Xenotropic_murine_leukemia_virus-related_virus&diff=774&oldid=prevLidewij: NL2010-06-17T12:09:04Z<p>NL</p>
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<p><b>New page</b></p><div>'''Xenotropic murine leukemia virus-related virus''' ('''XMRV''') is a [[gammaretrovirus]] that was first described in 2006.<ref name=pmid16609730/> XMRV has been isolated from human biological samples. Several reports have associated the virus with familial and sporadic [[prostate cancer]],<ref name=pmid17681844/><ref name="pmid19805305">{{cite journal |author=Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR |title=XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=106 |issue=38 |pages=16351–6 |year=2009 |month=September |pmid=19805305 |pmc=2739868 |doi=10.1073/pnas.0906922106}}</ref> but other reports do not find a link.<ref name=doi10.1371/><ref name=pmid18823818/> Similarly, a 2009 publication reported a possible association with [[chronic fatigue syndrome]],<ref name=pmid19815723/> but three other studies found no evidence of XMRV in patients or controls.<ref name=PLoSOne>{{cite journal |author=Erlwein O, Kaye S, McClure MO, ''et al.'' |title=Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome |journal=PLoS ONE |volume=5 |issue=1 |pages=e8519 |year=2010 |pmid=20066031 |pmc=2795199 |doi=10.1371/journal.pone.0008519}}</ref><ref name=Groom/><ref name=van_Kuppeveld/> It has not yet been established whether XMRV is a cause of either disease.<ref name=pmid20124560/> A German study found XMRV in 2%-3% of healthy controls and 10% of immunocompromised patients.<ref>http://www.cdc.gov/eid/content/16/6/pdfs/10-0066.pdf</ref><br />
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==Classification and genome==<br />
XMRV belongs to the virus family [[Retroviridae]] and the genus [[gammaretrovirus]]. It has a single-stranded RNA genome that replicates through a DNA intermediate. Its name refers to its close relationship with the [[murine leukemia virus]]es (“MuLVs”). The genome, approximately 8100 [[nucleotides]] in length, is 95% identical with several [[endogenous retrovirus]]es of mice, and is 93-94% identical with several [[exogenous]] mouse viruses.<ref name=pmid16609730/><br />
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Several XMRV genomic sequences have been published to date. These sequences are almost identical, an unusual finding<ref name=pmid20124560/> as retroviruses replicate their genomes with relatively low fidelity, leading to [[Quasispecies#Application to biological research|divergent viral sequences]] in a single host organism.<ref name=pmid20124560/><ref>{{cite journal |author=Voisin V, Rassart E |title=Complete genome sequences of the two viral variants of the Graffi MuLV: phylogenetic relationship with other murine leukemia retroviruses |journal=Virology |volume=361 |issue=2 |pages=335–47 |year=2007 |month=May |pmid=17208267 |doi=10.1016/j.virol.2006.10.045}}</ref><br />
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==History==<br />
XMRV was discovered by laboratories led by [[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 [[RNase L|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.<ref name=pmid11799394>{{cite journal |author=Carpten J, Nupponen N, Isaacs S, ''et al.'' |title=Germline mutations in the ribonuclease L gene in families showing linkage with HPC1 |journal=Nature Genetics |volume=30 |issue=2 |pages=181–4 |year=2002 |month=February |pmid=11799394 |doi=10.1038/ng823}}</ref> 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%.<ref name=pmid17681844>{{cite journal |author=Silverman RH |title=A scientific journey through the 2-5A/RNase L system |journal=Cytokine & Growth Factor Reviews |volume=18 |issue=5-6 |pages=381–8 |year=2007 |pmid=17681844 |pmc=2075094 |doi=10.1016/j.cytogfr.2007.06.012}}</ref><br />
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Silverman hypothesized that “the putative linkage of RNase L alterations to HPC might reflect enhanced susceptibility to a viral agent”,<ref name=pmid17681844/> leading to the discovery of XMRV.<br />
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==Reported disease associations and transmission==<br />
===Prostate cancer===<br />
Current reports in the scientific literature offer evidence both for and against an association of XMRV and prostate cancer. 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.<ref name=pmid16609730>{{cite journal |author=Urisman A, Molinaro RJ, Fischer N, ''et al.'' |title=Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant |journal=PLoS Pathogens |volume=2 |issue=3 |pages=e25 |year=2006 |month=March |pmid=16609730 |pmc=1434790 |doi=10.1371/journal.ppat.0020025}}</ref> Additionally, a 2009 study reported XMRV infection in 23% of subjects independent of the RNase L gene variation.<ref name="pmid19805305"/><br />
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However, researchers in Germany failed to find any 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.<ref name=doi10.1371>{{cite journal |author=Hohn O, Krause H, Barbarotto P, ''et al.'' |title=Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients |journal=Retrovirology |volume=6 |issue= |pages=92 |year=2009 |pmid=19835577 |pmc=2770519 |doi=10.1186/1742-4690-6-92}}</ref> Another German study found no XMRV association with non-familial (sporadic) prostate cancer,<ref name=pmid18823818>{{cite journal |author=Fischer N, Hellwinkel O, Schulz C, ''et al.'' |title=Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer |journal=Journal of Clinical Virology |volume=43 |issue=3 |pages=277–83 |year=2008 |month=November |pmid=18823818 |doi=10.1016/j.jcv.2008.04.016}}</ref> and no XMRV link was found in Irish prostate cancer patients with the R462Q mutation.<ref>{{cite journal |author=D'Arcy F, Foley R, Perry A, ''et al.'' |title=No evidence of XMRV in Irish prostate cancer patients with the R462Q mutation |journal=European Urology Supplements |volume=7 |pages=271 |month=March |year=2008 |doi=10.1016/S1569-9056(08)60798-8}}</ref><br />
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A causal role of XMRV in cancer has not been established,<ref name=pmid20124560>{{cite journal |author=Lee K, Jones KS |title=The path well traveled: using mammalian retroviruses to guide research on XMRV |journal=Molecular Interventions |volume=10 |issue=1 |pages=20–4 |year=2010 |month=February |pmid=20124560 |doi=10.1124/mi.10.1.5}}</ref> and XMRV does not appear to be capable of [[carcinogenesis|transforming cells]] directly.<ref name=pmid20007266>{{cite journal |author=Metzger MJ, Holguin CJ, Mendoza R, Miller AD |title=The prostate cancer-associated human retrovirus XMRV lacks direct transforming activity but can induce low rates of transformation in cultured cells |journal=Journal of Virology |volume=84 |issue=4 |pages=1874–80 |year=2010 |month=February |pmid=20007266 |doi=10.1128/JVI.01941-09 |pmc=2812358}}</ref> In prostate cancer, XMRV protein has been found in tumour-associated but nonmalignant [[stromal cell]]s, but not in the actual prostate cancer cells, raising the possibility that the virus may indirectly support [[tumorigenesis]].<ref name=pmid18201576>{{cite journal |author=McLaughlin-Drubin ME, Munger K |title=Viruses associated with human cancer |journal=Biochimica et Biophysica Acta |volume=1782 |issue=3 |pages=127–50 |year=2008 |month=March |pmid=18201576 |pmc=2267909 |doi=10.1016/j.bbadis.2007.12.005}}</ref> However, in another study, XMRV proteins and nucleic acids were found in malignant cells.<ref name="pmid19805305"/><ref name=pmid20124560/><br />
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===Chronic fatigue syndrome===<br />
In 2009, the [[Whittemore Peterson Institute]] , [[National Cancer Institute]] and [[Cleveland Clinic Lerner Research Institute| Cleveland Clinic]]<ref name=pmid19815723>{{cite journal |author=Lombardi VC, Ruscetti FW, Das Gupta J, ''et al.'' |title=Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome |journal=Science |volume=326 |issue=5952 |pages=585–9 |year=2009 |month=October |pmid=19815723 |doi=10.1126/science.1179052}}</ref> reported a possible association of XMRV with chronic fatigue syndrome. The study authors hypothesised that XMRV could cause CFS or be a passenger co-infection. Three follow-up studies<ref name=PLoSOne/><ref name=Groom>{{cite journal |doi=10.1186/1742-4690-7-10 |title=Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome |year=2010 |last1=Groom |first1=Harriet C T |last2=Boucherit |first2=Virginie C |last3=Makinson |first3=Kerry |last4=Randal |first4=Edward |last5=Baptista |first5=Sarah |last6=Hagan |first6=Suzanne |last7=Gow |first7=John W |last8=Mattes |first8=Frank M |last9=Breuer |first9=Judith |journal=Retrovirology |volume=7 |pages=10 |pmid=20156349 |pmc=2839973}}</ref><ref name=van_Kuppeveld>{{cite journal |author=van Kuppeveld FJ, Jong AS, Lanke KH, ''et al.'' |title=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 |journal=BMJ |volume=340 |issue= |pages=c1018 |year=2010 |pmid=20185493 |pmc=2829122 |doi= 10.1136/bmj.c1018|url=http://www.bmj.com/cgi/content/full/340/feb25_1/c1018}}</ref> failed to find evidence of XMRV in any of several hundred CFS patients or controls. Two reviews state reconciliation of these differences is necessary to investigate XMRV pathophysiology and treatment in CFS, and other possible XMRV-related illnesses, if they exist.<ref name=Baraniuk>{{Cite journal | last = Baraniuk | first = James N | title = Xenotropic Murine Leukemia Virus-Related Virus in Chronic Fatigue Syndrome and Prostate Cancer | journal = Current Allergy and Asthma Reports | publisher = Current Medicine Group LLC | date = 7 April 2010 | url = http://www.springerlink.com/content/416lq773u356024x/ | issn = 1529-7322 | doi = 10.1007/s11882-010-0106-2 | accessdate = 2010-04-25 | volume = 10 | pages = 210}}</ref><ref>Silverman, R. [http://www.nature.com/nrurol/journal/vaop/ncurrent/abs/nrurol.2010.77.html "The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome"], ''[[Nature Reviews Urology]]'', 1 June 2010.</ref> The reported association of XMRV and CFS has generated [[Whittemore Peterson Institute#Media coverage and controversy|media coverage and controversy]] amongst scientists and CFS patients alike.<br />
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===Transmission===<br />
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). Several authors have speculated that XMRV could be sexually transmitted,<ref>{{cite journal |author=Hong S, Klein EA, Das Gupta J, ''et al.'' |title=Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer |journal=Journal of Virology |volume=83 |issue=14 |pages=6995–7003 |year=2009 |month=July |pmid=19403677 |pmc=2704761 |doi=10.1128/JVI.00268-09}}</ref><ref>{{cite journal |author=Brower V |title=Is a retrovirus implicated in familial prostate cancer? |journal=Journal of the National Cancer Institute |volume=101 |issue=10 |pages=700–1 |year=2009 |month=May |pmid=19436028 |doi=10.1093/jnci/djp137}}</ref><ref>{{cite journal |first1=Peggy |last1=Eastman |month=January |year=2009 |title=Prostate Cancer: New Data Help Refine Risk Stratification |journal=Oncology Times |volume=31 |issue=2 |pages=32–3 |url=http://journals.lww.com/oncology-times/Fulltext/2009/01250/Prostate_Cancer__New_Data_Help_Refine_Risk.12.aspx |doi=10.1097/01.COT.0000345494.12042.f8 |doi_brokendate=2010-02-20}}</ref> but the mode of human transmission, if any, has not yet been investigated.<ref name=pmid20124560/> Both cell-associated and cell-free transmission have been reported ''in vitro''.<ref name=pmid19815723/> The virus has also been found in respiratory tracts and respiratory secretions of infected individuals<ref>http://www.cdc.gov/eid/content/16/6/pdfs/10-0066.pdf</ref><br />
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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."<ref name=HamSpec>[http://www.thespec.com/News/BreakingNews/article/748931 Virus leads Canadian Blood Services to ban certain donors] Joseph Hall, ''The Hamilton Spectator'', 06 April 2010.</ref> 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.<ref>{{cite web |author=National Center for Preparedness, Detection, and Control of Infectious Diseases (NCPDCID)|title=Xenotropic Murine Leukemia Virus-related Virus (XMRV)|url=http://www.cdc.gov/ncidod/dhqp/bp_xmrv.html|date of access=2010-02-21}}</ref><ref>http://online.wsj.com/article/SB10001424052702303450704575160081295988608.html?mod=googlenews_wsj</ref> The association of XMRV and CFS reported in ''Science'' prompted [[Health Canada]]<ref name=HamSpec/><ref>[http://www.cbc.ca/health/story/2010/04/07/blood-donations-chronic-fatigue-virus.html CBC]</ref><ref>[http://www.transfusionmedicine.ca/articles/canadian-blood-services-responds-possible-new-blood-safety-threat Canadian Blood Services Responds to Possible New Blood Safety Threat]</ref> and The [[Australian Red Cross Blood Service]]<ref>[http://www.donateblood.com.au/news-detail.aspx?IDDataTreeMenu=33&ID=390 Blood Service updates CFS donor policy]</ref> in 2010, to disallow blood donations from individuals with CFS.<br />
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==Drug studies==<br />
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A study in the ''[[Public Library of Science]]'' (PLoS) in 2010 concluded that four anti-HIV drugs also inhibit XMRV replication.<ref>Singh IR, Gorzynski JE, Drobysheva D, Bassit L, Schinazi RF, 2010 [http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0009948;jsessionid=B8A51A9FA99B373099C18EDB631467F3 Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome] PLoS ONE 5(4): e9948. doi:10.1371/journal.pone.0009948</ref> The drugs were two retroviral integrase inhibitors; [[raltegravir]] (Merck & Co., brand name Isentress), L-000870812 (Merck & Co.), and two nucleoside reverse transcriptase inhibitors; [[tenofovir disoproxil fumarate]] (Gilead Sciences, brand name Viread), and [[zidovudine]] (GlaxoSmithKline, azidothymidine (AZT)). Synergistic effects were reported when the drugs were used in combination.<br />
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==References==<br />
{{reflist}}<br />
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== External links ==<br />
* [http://www.aabb.org/documents/About_Blood/EID/xmrvfactsheet.pdf XMRV Fact Sheet, AABB.org (formerly American Association of Blood Banks)], Updated April 16, 2010<br />
* [http://www.cdc.gov/ncidod/dhqp/bp_xmrv.html DHHS Center for Disease Control and Prevention: XMRV Overview]<br />
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{{DEFAULTSORT:Xenotropic Murine Leukemia Virus-Related Virus}}<br />
[[Category:Retroviruses]]</div>Lidewij