The saga of XMRV: a virus that infects human cells but is not a human virus

Bob

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The saga of XMRV: a virus that infects human cells but is not a human virus
Maribel Arias and Hung Fan
Cancer Research Institute and Department of Molecular Biology and Biochemistry, University of California
Published online 9 April 2014
Emerging Microbes & Infections (2014) 3, e; doi:10.1038/emi.2014.25

http://www.nature.com/emi/journal/v3/n4/full/emi201425a.html

Full article available.
ABSTRACT
Xenotropic murine leukemia virus-related virus (XMRV) was discovered in 2006 in a search for a viral etiology of human prostate cancer (PC). Substantial interest in XMRV as a potentially new pathogenic human retrovirus was driven by reports that XMRV could be detected in a significant percentage of PC samples, and also in tissues from patients with chronic fatigue syndrome (CFS). After considerable controversy, etiologic links between XMRV and these two diseases were disproven. XMRV was determined to have arisen during passage of a human PC tumor in immunocompromised nude mice, by activation and recombination between two endogenous murine leukemia viruses from cells of the mouse. The resulting XMRV had a xentropic host range, which allowed it replicate in the human tumor cells in the xenograft. This review describes the discovery of XMRV, and the molecular and virological events leading to its formation, XMRV infection in animal models and biological effects on infected cells. Lessons from XMRV for other searches of viral etiologies of cancer are discussed, as well as cautions for researchers working on human tumors or cell lines that have been passed through nude mice, includingpotential biohazards associated with XMRV or other similar xenotropic murine leukemia viruses (MLVs).
 

Bob

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Maribel Arias and Hung Fan said:
XMRV was determined to have arisen during passage of a human PC tumor in immunocompromised nude mice, by activation and recombination between two endogenous murine leukemia viruses from cells of the mouse.
The above quote from the abstract is incorrect. Paprotka et al. later rebutted their own recombination paper, and we don't know how XMRV was created.
 

barbc56

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Does it make a difference if the origin of xmrv is different? If it does, what impact would this have on Lipkin's study?

Barb
 

Bob

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Does it make a difference if the origin of xmrv is different? If it does, what impact would this have on Lipkin's study?
Personally, I think we know very little about XMRV at this stage. Obviously, it can infect human tissue, and it has infected human tissue in the lab. That's about all we know. XMRV could have been created in the cell-line, as has been proposed, but the original evidence for that hypothesis was somewhat flawed. If I remember correctly, it was shown that XMRV might have evolved in the cell line, and so this means that there is still a possibility that it was created from the recombination of two alternative viruses (other than pre-XMRV1 and pre-XMRV2.) Alternatively, XMRV could have entered the cell line via external contamination. This possibility hasn't been explored very much, as far as I'm aware. I'm not sure how widespread XMRV contamination is thought to be in other cell lines, but I think there have been papers published about it.

I don't think any of this affects Lipkin's study, because he has pretty much shut down that line of research.
I'm not sure of the exact details, but the suggestion is that he found similar quantities of retrovirus in patients and control samples, in his latest study.
Perhaps if he found it in different quantities then he might have pursued it further, seeing as he's a virus hunter. But there again, maybe he thinks its too controversial.
 

Aerose91

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Can someone fill me in on the story about xmrv? I heard recently that it was disproven and is not a factor at all
 

Esther12

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Can someone fill me in on the story about xmrv? I heard recently that it was disproven and is not a factor at all
That's a pretty good summary.

Could go into more detail, but there's currently no good reason to think XMRV is related to CFS.
 

Esther12

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Is xmrv even a real virus?
Errr... depends what you mean by 'real virus' I think. It's thought that the positive samples were a result of contamination, and that XMRV is not circulating in the human population. Overall: not something that's worth investigating unless you have an academic interest in viruses imo.