Hence a positive response to a IAP assay may well just indicate XMRV or PMLV infection.
FORBES: Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed
In the latest work, the team, from London and the University of Oxford, used DNA sequencing methods to study XMRV.
Morever, only 4 percent of controls in the Mikovits study tested positive for XMRV, while 67 percent of patients tested positive.
The association between XMRV and mouse DNA in this study is imperfect whereas in a contaminant scenario it would not be.
FORBES: Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed
This of course means that any conclusion made by PCR alone regarding the association of XMRV and mouse DNA is profoundly unsafe.
FORBES: Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed
The Centers for Disease Control and Prevention, among other groups, published studies reporting they didn't find XMRV in chronic fatigue syndrome patients.
After the 2009 study, other published studies showed that some anti-retrovirals approved for use in HIV might also be effective against XMRV.
The authors theorise that this may be due to the inability of their PCR assay to detect XMRV in low copy numbers.
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Moving on, the Mikovits study found antibody reactions to XMRV in patients.
The only study which has detected XMRV in prostate cancer using primers set for unique sequences in the XMRV genome is Schlaberg et al 2009 (2).
FORBES: Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed
The researchers reported they found the retrovirus XMRV in a majority of 101 patients with chronic fatigue syndrome, a debilitating condition that involves cognitive dysfunction and severe pain.
If XMRV were contamination, one would expect an equal distribution.
Secondly the presence of a recombinant with a different gag sequence is entirely consistent with the behaviour of XMRV-related viruses in vivo and is to expected in tumour tissue (7).
FORBES: Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed
Patients responding to anti-retrovirals would put a serious kink in the XMRV contamination theory, which is one reason some believe that these researchers are determined to get patients off them.
The detection rate by PCR is in line with that reported by Danielson et al but some 400% lower than that achieved by IHC using XMRV specific probes (2, 3).
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Other papers found that substances used as part of the process to detect XMRV might be contaminated, raising the possibility that this may explain the positive findings in the 2009 Science paper.
One must also point out that Robinson et al did not find higher rates of XMRV infection in cancerous versus non cancerous sequences which is a serious departure from the results of other workers.
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"There have now been a number of attempts which have failed to find the retrovirus in other samples, and this research suggests that in fact XMRV is probably a contamination from mouse DNA, " he said.
Indeed, the clone reported by the authors which contained a 24 base pair deletion in glycogag would be a classic example of a viral variant caused by the recombination of XMRV and an endogenous MLV virus.
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As PCR is by some considerable margin the least sensitive method for detecting XMRV in prostate cancer (2, 3) and chronic fatigue syndrome (4) no association between the presence of mouse DNA and XMRV can be safely made.
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The authors expressed surprise that their PCR approach produced gag sequences which did not contain the 24-nt deletion characteristically present in the XMRV sequences cloned to date, as they expected their primers to be specific to VP62 gag.
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Indeed, one would argue that the authors (if aware of recent research conducted by Danielson et al 2010) (8) should have been surprised that primer sequences that they believed were specific to XMRV gag would have produced any product at all.
FORBES: Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed
It is therefore something of a mystery why researchers concerned about mouse contamination did not engage in a literature search to establish whether the primers used in their experiments were in fact specific to XMRV sequences which are unique to the virus.
FORBES: Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed
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