No Surprise - news that even our Utah XMRV/MLV expert was finding XMRV more complicated than expected probably should have come as no surprise...broken timelines have been maybe the most consistent thing we've been able to observe with XMRV. Consider these
(*)WPI, with Glaxo Smith Kline reportedly on board, was reported to expect treatment trials to begin within six months of the Science publication.
(*)At the CFSAC meeting late last year Dr. Coffin thought we'd have the answer 'within six months'
(*)The antibody tests were promised and promised....but eventually they did arrive (so there's hope
)
(*)The WPI started with one set of methods in the Science paper and then brought forth an improved set about five months later
(*)Dr. Singh's study is taking a bit longer than expected because - a PR Forum member was just told -it's more complicated than expected
(*)Dr LeGrice and Dr. Glynnis just a month ago thought Phase II would wrap up about 10 days ago....
Who wants to bet on Phase III being wrapped by New Years? XMRV is clearly complicated. It's definitely past time to stop expecting anything to happen on a timeline. All we know for sure is that the results won't be done until they are done - and not a second before.
International Conference Rita on the PR Forums somehow found some interesting XMRV abstracts in the 11 Symposium on Antiviral Drug Resistance - demonstrating again that XMRV is getting in anywhere it can.
XMRV in Immune Cells - One from the National Cancer Institute sought to explain an interesting dilemma - research done after the WPI's Science paper indicates that XMRV is basically knocked down and rendered non-infectious by the APOBEC3 enzyme in the immune cells in the blood the WPI found it in. (The amino acids the enzyme replaces in XMRV makes it impossible for XMRV to replicate.) Yet after digging XMRV out of these immune cells the WPI was able to grow the virus and replicate it! If that enzyme had rendered XMRV inert, so to speak, how was the WPI able to get it to replicate again? These researchers found that XMRV could replicate in PBMC's only if the APOBEC enzyme was inactivated. However, if they cultured the cells with 'canine indicator cells' they could recover infectious virus. This suggests to me, a laymen, way in over his head, that there are substances that can help XMRV bypass the APOBEC3 enzyme.
However, these researchers suggested that this does not happen in the blood in the body, and that at least as regards replication, the immune cells tested thus far are essentially a dead end for XMRV. (Hence the search for a different viral reservoir)
One of the most interesting part of this study was the ease with which they did it. They simply infected cells with XMRV and monitored virus production using quantitative PCR. It's clearly much easier to purposefully infect cells and then detect the virus again than it is to find it in the blood.
Dr Coffin Gets Down to Work! - Dr. Coffin's at Tufts and the National Cancer Institute (again) have been taking on one of thorniest problems - how to distinguish XMRV from mouse DNA or from an endogenous retrovirus.
An endogenous retrovirus is a retrovirus that, sometime in the distant past, inserted parts of itself into the genome of an organism. The genomes of inbred mice in labs, in particular, are swarming with degraded non-infectious MLV gene sequences. The right bit of mouse DNA contaminating a sample could,therefore, look like XMRV. The WPI was able to isolate the whole virus - indicating they did not discover an endogenous retrovirus - but no one else has.
A very specific PCR assay Dr Coffin developed for XMRV has not found it all in inbred or wild mice - suggesting, as Dr. Mikovits reported, that it is unique to humans. They developed another assay that distinguishes between XMRV and endogenous MLV retroviruses - thus enabling them to quickly tell if a gene sequence belongs to XMRV, an endogenous retrovirus or from mouse DNA. Plus they've developed another PCR assay that focuses on mouse 'DAN' contamination.
It appears that researchers are becoming ever more effective at determining when an XMRV result is real and when it actually reflects something else. These tests will be be very helpful (a) to researchers such as Dr. Alter and Dr. Hansen who have found gene sequences that are XMRV-like but have pMLV characteristics and (b) to clearing up the contamination question. Basically it appears Dr. Coffin now knows XMRV when he finds it.
