{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:32:49Z","timestamp":1790019169747,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T00:00:00Z","timestamp":1429228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A11951"],"award-info":[{"award-number":["A11951"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000651","name":"Leukaemia and Lymphoma Research","doi-asserted-by":"publisher","award":["10022"],"award-info":[{"award-number":["10022"]}],"id":[{"id":"10.13039\/501100000651","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB\/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9\/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD\/SCID\/\u03b3Cnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies.<\/jats:p>","DOI":"10.3390\/v7042014","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T11:09:30Z","timestamp":1429268970000},"page":"2014-2029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo"],"prefix":"10.3390","volume":"7","author":[{"given":"Asif","family":"Naseer","sequence":"first","affiliation":[{"name":"Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Terry","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Gilroy","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kilbey","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciorsdaidh","family":"Watts","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Mackay","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Bell","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Glasgow, Garscube Estate, Bearsden Road,  G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Mason","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road,  Bearsden, G61 1BD Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Blyth","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road,  Bearsden, G61 1BD Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewan","family":"Cameron","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Glasgow, Garscube Estate, Bearsden Road,  G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Neil","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1073\/pnas.70.3.859","article-title":"A type-C virus in human rhabdomyosarcoma cells after inoculation into NIH Swiss mice treated with antithymocyte serum","volume":"70","author":"Todaro","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/bjc.1979.5","article-title":"C-type virus particles in human urogenital tumours after heterotransplantation into nude mice","volume":"39","author":"Wunderli","year":"1979","journal-title":"Br. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.coviro.2012.06.009","article-title":"Recombinant origin, contamination, and de-discovery of XMRV","volume":"2","author":"Cingoz","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.1205292","article-title":"Recombinant origin of the retrovirus XMRV","volume":"333","author":"Paprotka","year":"2011","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12585","DOI":"10.1128\/JVI.01726-08","article-title":"Identification of gammaretroviruses constitutively released from cell lines used for human immunodeficiency virus research","volume":"82","author":"Takeuchi","year":"2008","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1128\/JVI.06717-11","article-title":"Detection of murine leukemia virus in the Epstein-Barr virus-positive human B-cell line JY, using a computational RNA-Seq-based exogenous agent detection pipeline, PARSES","volume":"86","author":"Lin","year":"2012","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1128\/JVI.02570-14","article-title":"High-throughput RNA sequencing-based virome analysis of 50 lymphoma cell lines from the Cancer Cell Line Encyclopedia project","volume":"89","author":"Cao","year":"2015","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"617","DOI":"10.4161\/cbt.12.7.15955","article-title":"Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts","volume":"12","author":"Zhang","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23465","DOI":"10.1074\/jbc.M114.557447","article-title":"Umbilical cord mesenchymal stem cells suppress host rejection: The role of the glycocalyx","volume":"289","author":"Gesteira","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nature13556","article-title":"Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity","volume":"514","author":"Marusyk","year":"2014","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8750","DOI":"10.18632\/oncotarget.2373","article-title":"Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer","volume":"5","author":"Dobbin","year":"2014","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3389\/fonc.2013.00156","article-title":"Infection of Xenotransplanted Human Cell Lines by Murine Retroviruses: A Lesson Brought Back to Light by XMRV","volume":"3","author":"Hempel","year":"2013","journal-title":"Front Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1128\/JVI.06073-11","article-title":"Xpr1 is an atypical G-protein-coupled receptor that mediates xenotropic and polytropic murine retrovirus neurotoxicity","volume":"86","author":"Vaughan","year":"2012","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e42321","DOI":"10.1371\/journal.pone.0042321","article-title":"XMRV induces cell migration, cytokine expression and tumor angiogenesis: Are 22Rv1 cells a suitable prostate cancer model?","volume":"7","author":"Stieler","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7124","DOI":"10.1038\/sj.onc.1203202","article-title":"A full-length Cbfa1 gene product perturbs T-cell development and promotes lymphomagenesis in synergy with myc","volume":"18","author":"Vaillant","year":"1999","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11263","DOI":"10.1158\/0008-5472.CAN-07-3016","article-title":"Runx2 disruption promotes immortalization and confers resistance to oncogene-induced senescence in primary murine fibroblasts","volume":"67","author":"Kilbey","year":"2007","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/bjc.1990.233","article-title":"Gene expression in oestrogen-dependent human breast cancer xenograft tumours","volume":"62","author":"Thompson","year":"1990","journal-title":"Br. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0092-8674(74)90008-7","article-title":"Type C viruses of baboons: Isolation from normal cell cultures","volume":"2","author":"Todaro","year":"1974","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1126\/science.204014","article-title":"Genetic mapping of xenotropic leukemia virus-inducing loci in two mouse strains","volume":"199","author":"Kozak","year":"1978","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1099\/0022-1317-65-2-317","article-title":"Phenotypic mixing of retroviruses in mitogen-stimulated lymphocytes: Analysis of xenotropic and defective endogenous mouse viruses","volume":"65","author":"Stoye","year":"1984","journal-title":"J. Gen. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e25592","DOI":"10.1371\/journal.pone.0025592","article-title":"No detection of XMRV in blood samples and tissue sections from prostate cancer patients in Northern Europe","volume":"6","author":"Stieler","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1084\/jem.152.1.219","article-title":"Genetic mapping of xenotropic murine leukemia virus-inducing loci in five mouse strains","volume":"152","author":"Kozak","year":"1980","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1128\/jvi.60.3.980-986.1986","article-title":"Nonecotropic murine leukemia viruses in BALB\/c and NFS\/N mice: Characterization of the BALB\/c Bxv-1 provirus and the single NFS endogenous xenotrope","volume":"60","author":"Hoggan","year":"1986","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/0042-6822(87)90298-4","article-title":"Nucleotide conservation of endogenous ecotropic murine leukemia proviruses in inbred mice: Implications for viral origin and dispersal","volume":"157","author":"King","year":"1987","journal-title":"Virology"},{"key":"ref_25","first-page":"25","article-title":"Humanized SCID mouse models for biomedical research","volume":"324","author":"Pearson","year":"2008","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e87475","DOI":"10.1371\/journal.pone.0087475","article-title":"Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia","volume":"9","author":"Leonard","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0092-8674(03)00423-9","article-title":"DNA deamination mediates innate immunity to retroviral infection","volume":"113","author":"Harris","year":"2003","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e74427","DOI":"10.1371\/journal.pone.0074427","article-title":"Utilization of replication-competent XMRV reporter-viruses reveals severe viral restriction in primary human cells","volume":"8","author":"Sturzel","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.coviro.2014.03.006","article-title":"Interferon-stimulated genes: Roles in viral pathogenesis","volume":"6","author":"Schoggins","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"ref_30","first-page":"219","article-title":"Innate immune responses to hepatitis C virus","volume":"369","author":"Schoggins","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.coviro.2011.10.008","article-title":"Interferon-stimulated genes and their antiviral effector functions","volume":"1","author":"Schoggins","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/ni735","article-title":"B cells and professional APCs recruit regulatory T cells via CCL4","volume":"2","author":"Bystry","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1384S","DOI":"10.1093\/jn\/130.5.1384S","article-title":"Integrative aspects of zinc transporters","volume":"130","author":"Cousins","year":"2000","journal-title":"J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"42741","DOI":"10.1074\/jbc.M207096200","article-title":"Two highly conserved glutamate residues critical for type III sodium-dependent phosphate transport revealed by uncoupling transport function from retroviral receptor function","volume":"277","author":"Bottger","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.celrep.2013.05.035","article-title":"Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans","volume":"3","author":"Giovannini","year":"2013","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5725","DOI":"10.1093\/jxb\/eru314","article-title":"Phosphate and zinc transport and signalling in plants: Toward a better understanding of their homeostasis interaction","volume":"65","author":"Bouain","year":"2014","journal-title":"J. Exp. Bot."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1574-6968.2008.01386.x","article-title":"Expression of the PitA phosphate\/metal transporter of Escherichia coli is responsive to zinc and inorganic phosphate levels","volume":"289","author":"Jackson","year":"2008","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e20874","DOI":"10.1371\/journal.pone.0020874","article-title":"Identification of replication competent murine gammaretroviruses in commonly used prostate cancer cell lines","volume":"6","author":"Sfanos","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8595","DOI":"10.1073\/pnas.1401215111","article-title":"Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis","volume":"111","author":"Triviai","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.virol.2014.03.006","article-title":"XMRV low level of expression in human cells delays superinfection interference and allows proviral copies to accumulate","volume":"456\u2013457","author":"Laurent","year":"2014","journal-title":"Virology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000059711","article-title":"Egr1 transcription factor: Multiple roles in prostate tumor cell growth and survival","volume":"23","author":"Adamson","year":"2002","journal-title":"Tumour Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nature12862","article-title":"Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity","volume":"505","author":"Schoggins","year":"2014","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7309","DOI":"10.1128\/jvi.69.11.7309-7314.1995","article-title":"The lytic cycle of Epstein-Barr virus in the nonproducer Raji line can be rescued by the expression of a 135-kilodalton protein encoded by the BALF2 open reading frame","volume":"69","author":"Decaussin","year":"1995","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/4\/2014\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:44:54Z","timestamp":1760215494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/4\/2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,17]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4]]}},"alternative-id":["v7042014"],"URL":"https:\/\/doi.org\/10.3390\/v7042014","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,17]]}}}