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XMRV: not a mousy virus

Jemal

Senior Member
Messages
1,031
In retrospect, the method used in most studies for detection of XMRV, almost exclusively nested PCR amplification, has been a rather unlucky choice. In clinical virology, a putative virus infection is usually probed with a serological assay, although real time PCR assays are currently in use for infections in which a high copy number of viral nucleic acid (RNA or DNA) is known to correlate with disease. A simple detection PCR is rarely the first method of choice for several reasons, including the danger of getting false positives due to contamination. Serological assays for XMRV are currently being developed, and will be much needed to distinguish genuine infected patients from contamination cases. Serology will be more informative than running a control PCR for mouse DNA as contamination by XMRV particles (e.g. from protein preparations or contaminated cell cultures) will not show mouse DNA, other than the viral genome.

http://download.journals.elsevierhealth.com/pdfs/journals/0929-6646/PIIS0929664611600429.pdf

Same Dutch virology professor that launched a hypothesis that XMRV might have been introduced through vaccines:
http://www.frontiersin.org/virology/10.3389/fmicb.2010.00147/full
 

Spring

Senior Member
Messages
133
Location
Netherlands
So glad there are two professors in the Netherlands doing 'something' with XMRV! Although I had to read about this on this forum...
 

Jemal

Senior Member
Messages
1,031
So glad there are two professors in the Netherlands doing 'something' with XMRV! Although I had to read about this on this forum...

Yeah, I am glad about this as well (I am Dutch too).
It's a pretty neutral article, which is nice. And their hypothesis that the virus might have been introduced through vaccines could spark great controversy and seemingly they are not afraid of that.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Thanks Jemal, very interesting.

I'm looking forward to those serological assays being produced seeing as they "should be used to identify genuinely XMRV-infected patients that can subsequently be studied to elucidate the replication and pathogenic properties of XMRV infection in humans."

If the use of serological assays is good science, then it begs the question: Why haven't they been used already?

Interesting that the authors say that human genome integration has been demonstrated (despite the suggestion that the study only detected integration into a cell line genome) but I didn't quite understand this paragraph:

"In situ fluorescent hybridization of prostate cancer tissue has detected XMRV proviral genomes that correlated with neutralizing antibody reactivity and/or PCR results in patients.9"

ref:
9. Arnold RS, Makarova NV, Osunkoya AO, et al. XMRV infection in patients with prostate cancer: novel serologic assay and correlation with PCR and FISH. Urology 2010; 75:75561.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I just found a handy interesting table listing all of the XMRV studies:

http://www.aabb.org/resources/bct/eid/Documents/xmrvtable.pdf

It's interesting looking through the list as a reminder of the number of positive prostate cancer studies.


But also interesting is this one that I hadn't seen before:

High prevalence of an IgG response against murine leukemia virus (MLV) in patients with psoriasis
Jean-Pierre Mols, Jean-Christophe Hadi and Jean-Jacques Guilhou
Received 27 January 2003; revised 28 April 2003; accepted 14 May 2003. ; Available online 29 July 2003
http://www.sciencedirect.com/science/article/pii/S0168170203001370

I'm not sure why this study was included in the list because they don't say that they detected either XMRV or PMRV, but suggest that they are looking at MLV-like human endogenous retroviral (HERVs) particles.

Strangely, the IgG response rate in this study gives almost identical results: 86% vs 8% (patients vs controls) as did the Alter/Lo study for PMRV's (86.5% vs 6.8%): "In addition, the IgG response was dramatically increased in psoriasis (86 vs. 8%, respectively, P<0.0001)."

But the detection of antibodies in this study was 91 vs. 53% (patients vs controls), suggesting that these are indeed MLV-like endogenous human retroviral particles (or maybe the possibility that they are detecting ubiquitous exogenous MLV viruses?)

Interesting food for thought.
 

RedRuth

Senior Member
Messages
143
She's almost certainly right though there are also potential problems with ELISA and Western blotting (something I do a lot of) After reading the Science paper I thought the western blotting was not very impressive at all.