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  • 1
    Publication Date: 2011-06-02
    Description: The retrovirus XMRV (xenotropic murine leukemia virus-related virus) has been detected in human prostate tumors and in blood samples from patients with chronic fatigue syndrome, but these findings have not been replicated. We hypothesized that an understanding of when and how XMRV first arose might help explain the discrepant results. We studied human prostate cancer cell lines CWR22Rv1 and CWR-R1, which produce XMRV virtually identical to the viruses recently found in patient samples, as well as their progenitor human prostate tumor xenograft (CWR22) that had been passaged in mice. We detected XMRV infection in the two cell lines and in the later passage xenografts, but not in the early passages. In particular, we found that the host mice contained two proviruses, PreXMRV-1 and PreXMRV-2, which share 99.92% identity with XMRV over 〉3.2-kilobase stretches of their genomes. We conclude that XMRV was not present in the original CWR22 tumor but was generated by recombination of two proviruses during tumor passaging in mice. The probability that an identical recombinant was generated independently is negligible (~10(-12)); our results suggest that the association of XMRV with human disease is due to contamination of human samples with virus originating from this recombination event.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278917/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278917/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paprotka, Tobias -- Delviks-Frankenberry, Krista A -- Cingoz, Oya -- Martinez, Anthony -- Kung, Hsing-Jien -- Tepper, Clifford G -- Hu, Wei-Shau -- Fivash, Matthew J Jr -- Coffin, John M -- Pathak, Vinay K -- P30 CA093373/CA/NCI NIH HHS/ -- R01CA150197/CA/NCI NIH HHS/ -- R37 CA 089441/CA/NCI NIH HHS/ -- R37 CA089441/CA/NCI NIH HHS/ -- R37 CA089441-11/CA/NCI NIH HHS/ -- ZIA BC011339-02/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Jul 1;333(6038):97-101. doi: 10.1126/science.1205292. Epub 2011 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Viral Mutation Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21628392" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor/*virology ; DNA Contamination ; DNA, Viral/analysis ; Endogenous Retroviruses/genetics ; Fatigue Syndrome, Chronic/virology ; Gammaretrovirus/*genetics ; Genes, env ; Genes, gag ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Polymerase Chain Reaction ; Prostatic Neoplasms/*virology ; Proviruses/genetics/isolation & purification ; *Recombination, Genetic ; Transplantation, Heterologous ; Xenotropic murine leukemia virus-related virus/*genetics/*isolation & ; purification
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-09-24
    Description: Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody. Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement, and reactivity was similar among CFS subjects and negative controls. These results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299483/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299483/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, Graham -- Glynn, Simone A -- Komaroff, Anthony L -- Mikovits, Judy A -- Tobler, Leslie H -- Hackett, John Jr -- Tang, Ning -- Switzer, William M -- Heneine, Walid -- Hewlett, Indira K -- Zhao, Jiangqin -- Lo, Shyh-Ching -- Alter, Harvey J -- Linnen, Jeffrey M -- Gao, Kui -- Coffin, John M -- Kearney, Mary F -- Ruscetti, Francis W -- Pfost, Max A -- Bethel, James -- Kleinman, Steven -- Holmberg, Jerry A -- Busch, Michael P -- Blood XMRV Scientific Research Working Group (SRWG) -- N01 HB-57181/HB/NHLBI NIH HHS/ -- N01HB57181/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2011 Nov 11;334(6057):814-7. doi: 10.1126/science.1213841. Epub 2011 Sep 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Blood Systems Research Institute and University of California, San Francisco, San Francisco, CA 94118, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21940862" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Viral/blood ; Blood/*virology ; Blood Specimen Collection ; Cell Line ; Coculture Techniques ; False Positive Reactions ; Fatigue Syndrome, Chronic/*virology ; Female ; Humans ; Laboratories ; Male ; Polymerase Chain Reaction ; Reproducibility of Results ; Retroviridae Infections/virology ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; Viremia ; Virus Replication ; Xenotropic murine leukemia virus-related virus/genetics/immunology/*isolation & ; purification/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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