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Metzger Dec 09 XMRV Can Induce Low Rates of Transformation in Cultured Cells

Discussion in 'XMRV Research and Replication Studies' started by leelaplay, Mar 22, 2010.

  1. leelaplay

    leelaplay member

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    [if: I don't think we've seen this before. Apologies if we have - I did search + visually scan]

    Journal of Virology, February 2010, p. 1874-1880, Vol. 84, No. 4
    0022-538X/10/$012.00+0 doi:10.1128/JVI.01941-09
    Copyright 2010, American Society for Microbiology. All Rights Reserved.

    The Prostate Cancer-Associated Human Retrovirus XMRV Lacks Direct Transforming Activity but Can Induce Low Rates of Transformation in Cultured Cells{triangledown}
    Michael J. Metzger, Christiana J. Holguin, Ramon Mendoza, and A. Dusty Miller*

    Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024

    Received 13 September 2009/ Accepted 30 November 2009

    The human retrovirus XMRV (xenotropic murine leukemia virus-related virus) is associated with prostate cancer, but a causal relationship has not been established. Here, we have used cultured fibroblast and epithelial cell lines to test the hypothesis that XMRV might have direct transforming activity but found only rare transformation events, suggestive of indirect transformation, even when the target cells expressed the human Xpr1 cell entry receptor for XMRV. Characterization of cells from three transformed foci showed that all were infected with and produced XMRV, and one produced a highly active transforming virus, presumably generated by recombination between XMRV and host cell nucleic acids. Given the sequence similarity of XMRV to mink cell focus-forming (MCF) viruses and the enhanced leukemogenic activity of the latter, we tested XMRV for related MCF-like cytopathic activities in cultured mink cells but found none. These results indicate that XMRV has no direct transforming activity but can activate endogenous oncogenes, resulting in cell transformation. As part of these experiments, we show that XMRV can infect and be produced at a high titer from human HT-1080 fibrosarcoma cells that express TRIM5{alpha} (Ref1), showing that XMRV is resistant to TRIM5{alpha} restriction. In addition, XMRV poorly infects NIH 3T3 cells expressing human Xpr1 but relatively efficiently infects BALB 3T3 cells expressing human Xpr1, showing that XMRV is a B-tropic virus and that its infectivity is regulated by the Fv1 mouse locus.

    * Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109-1024. Phone: (206) 667-2890. Fax: (206) 667-6523. E-mail: dmiller@fhcrc.org

    {triangledown} Published ahead of print on 9 December 2009.

    Journal of Virology, February 2010, p. 1874-1880, Vol. 84, No. 4
    0022-538X/10/$012.00+0 doi:10.1128/JVI.01941-09
    Copyright 2010, American Society for Microbiology. All Rights Reserved.
     
  2. Dolphin

    Dolphin Senior Member

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    Don't mean/like to criticise as it's great that you post articles and I love the discussions that follow, but this isn't really a ME/CFS-specific paper and might be more suitable in:
     
  3. leelaplay

    leelaplay member

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    I love how tactful you are Tom. Good idea - sometimes I forget that there's a separate xmrv section. I'll ask an admin to move it.
     
  4. _Kim_

    _Kim_ Guest

  5. leelaplay

    leelaplay member

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  6. rebecca1995

    rebecca1995 Apple, anyone?

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    Northeastern US
    Thank you, IF and Kim for posting this! It's heartening that even as the politics surrounding ME/CFS play out in their usual sordid way, real scientists are quietly going about the work of characterizing XMRV. For that we can thank the male reproductive organs!

    We are prostrate to the prostate!
    [​IMG]
    "We are not worthy, we are not worthy, we are not worthy!"
     
  7. leelaplay

    leelaplay member

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    too funny Rebecca!
     
  8. MEKoan

    MEKoan Senior Member

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    :D :tear: :D :tear: :D :tear: :D :tear: :D
     
  9. Cort

    Cort Phoenix Rising Founder

    Well done Rebecca!
     
  10. rebecca1995

    rebecca1995 Apple, anyone?

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    Northeastern US
    Thanks, folks! I've been waiting for a chance to use that graphic! Too bad I couldn't find one with a lingam, too...:Retro tongue:
     
  11. Adam

    Adam

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    Sheffield UK
    For a second there I thought I was looking at a shaven testicle with ears that someone was about to lift off the ground (note - no gloves - can't be hygienic)

    Glad it was a Buddhist.
     

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