LONG AND SPECULATIVE POST ALERT
I don't believe that its a good idea to speculate wildly about what these results mean, especially when knowledge and expertise is limited. Best to leave that to the experts.
But, I just can't help myself.
Following on from Alex's comments earlier in the thread, I can't help wondering if there is any way of reconciling the findings of 'both sides' if they are both correct?
For the sake of argument, lets assume all of the following findings are true :
From the positive studies;
XMRV found in 22% of patients with aggressive prostate cancer;
XMRV found in approx 65 to 95% of PWC's;
A very similar PMLV was found in the Lo/Alter patients but 'not XMRV';
XMRV found in 4 to 7% of 'healthy' controls;
While initially there appeared to little genetic diversity in patient samples of XMRV, there are also now indications that the diversity is greater than previously thought.
From the 'contamination' studies
Commonly used lab mouse species now known to host a variety of ERVs and MuLVs;
Contamination of labs working with mice now appears to be more widespread than previously assumed;
The 22Rv1cell line was created, some time before 1999 as far as I can see, as a 'human prostatic carcinoma xenograft serially propagated in mice';
the MuLV found in this cell line is, by statistical analysis, ancestral to XMRV;
the MuLV found in the cell line has greater genetic diversity than that found in the two patient samples.
I know little about population genetics or retroviruses but from what I can pick up I'm assuming that a retrovirus accumulates genetic diversity by recombination with other viruses and the host DNA and therefore a retrovirus circulating in the population should show greater diversity between patient samples than that found in a laboratory contaminant?
Statistical analysis can demonstrate where a sample fits on the phylogenetic tree, that is, whether a given sample is derived from or ancestral to another. The 22Rv1cell line virus appears to be closely related to and ancestral to the patient samples.
Another way of looking at this relationship however is that being ancestral to another sample or other retrovirus is also a function of time. Presumably, once the cell line was created it is then cloned and the XMRV is 'immortalised', that is the genetic structure is 'fixed' at the time the cell line was created and as such is akin to a 'viral fossil'. This being the case, the only thing we can definitively conclude from the Hue paper is that the 22Rv1cell line XMRV dates from an earlier time period than the patient samples (necessarily some time before 1999).
Further, assuming that contamination is much more prevalent than previously thought and that in 1999 and before the potential for contamination was greater (being unaware of the scale of the problem) it logically follows that contamination of cell lines by MuLVs was fairly common. If we also assume that the incidence of XMRV in aggressive prostate cancer runs at around 25%, then a cell line consisting on a xenograft of human prostate cancer tissues and 'serially propagated in mice' could quite easily contain a 'swarm' consisting of many MuLVs from many mice, the strain of XMRV circulating in the population at the time donated by the PC patient at the time the cell line was created and potentially hybrids of the two. Didn't one of Dusty Miller's papers state 'the virus found in the 22Rv1cell line IS XMRV'.
Two scenarios spring to mind :
(a) The 22Rv1cell line XMRV is indeed ancestral to that found in patients as it was introduced into the cell line from the human population at a much earlier time. The XMRV found in patients shows less genetic diversity because :
there is less scope for hybridisation in a human host compared to the procedure that produced the 22Rv1cell line;
while the WPI sample came from various regions, at least some of them came from an outbreak cluster where you would expect the same strain of XMRV to be present.
(b) What happens when you culture patient samples using the 22Rv1cell line and then test for XMRV? Depending on what you are looking for or hoping to exclude you might find :
the 22Rv1cell line XMRV only suggesting contamination;
the patient's own strain of XMRV which would be a descendant of the 22Rv1cell line XMRV but should be more dissimilar to it;
a new hybrid of the 22Rv1cell line XMRV and the patient's own XMRV which would be directly descended from the 22Rv1cell line and also very similar;
all of the above, a closely related XMRV/PMLV swarm;
or your controls against MuLV contamination are so broad that they exclude finding any XMRV.
