Discussion in 'XMRV Research and Replication Studies' started by Aftermath, Oct 13, 2009.
Interesting post Advocate. Thanks.
JHK not found in CFS
Just to be clear, Dr. Grossman did not find what he calls the JHK retrovirus in CFS patients. He found it in a human cell line used for research. CFS patients had antibodies which reacted to JHK. Since JHK is 96% genetically identical to XMRV, it's not surprising that a CFS patient infected with XMRV would have cross-reactive antibodies to JHK.
Seems like the technology has changed so much in recent years, it might be hard to say what exactly was found in '91 and '01 - the existence of CAV and JHK was clearly never confirmed, since there are still only the 3 known human infectious retroviruses. Perhaps they were seeing evidence of XMRV but misinterpreting it. The Mikovitz XMRV study seems to be in a class by itself, since it's looking at a known retrovirus, rather than claiming to discover a new one.
JHK has been confirmed
The existence of JHK has been confirmed, it's just never been found in a person, so it couldn't (yet) be classified as an infectious human retrovirus.
JerryH, that link goes to a MLV DG-75 - is that JHK? But either way you're right, I should have said they were never confirmed as a human infectious retrovirus.
I appreciate your input jerryH and fresheyes. If JHK is not confirmed as infectious then I must be wrong and I shouldn't have stated it is. I don't mind being wrong, I just want the truth.
XMRV is the only infectious human retrovirus that has been confirmed in CFS then, right?
I'm glad that the WPI made a statement about XMRV not being CAV. At least now we know.
Hi teejkay. Well, yes, XMRV is the first known infectious human retrovirus to be found associated with CFS - though we probably still can't say "confirmed" until at least one more study comes out!
You're right, though, in your earlier post where you say that WPI is acting as if those previous discoveries were mistaken, which it seems like we really don't know yet either. We all know the ugly history of CFS research. Hopefully in the future all these questions will be answered.
Thanks fresheyes. I feel like I understand the situation better now.
I reformatted the points the WPI make about the differences between CAV and XMRV.
Here's the link to their paragraph:
These are the main points:
CAV is not a gamma (type C) retrovirus, because of its diameter, morphology, formation and location of intracellular virions.
XMRV is a type C retrovirus.
All CAV particles are the same shape and size, 46-50 nm. No forms budding from the cytoplasmic membranes are observed.
XMRV shows a budding type C retrovirus of 90-100 microns.
CAV-infected cells could be characterized by electron-dense circular virions, some with electron-luscent cores and others with electron-dense cores, associated with the rough endoplasmic reticulum and inside large abnormally distended mitochondria in the cells. No extracellular virus is observed.
XMRV Gamma (type C) retroviruses are 90-1100 uM as shown in Lombardi et al and all are shown to consist of electron dense cores and specifically to bud extra-cellularly not intracellularly.
The data describes in the De Freitas patent can be found at:http://www.ncf-net.org/forum/revelations.html These data are indisputable that XMRV is NOT the retrovirus described by De Freitas et al.
Well, De Freitas et al do say that CAV is infectious -
- so this brings us back to having 2 different infectious human retroviruses, and both may be murine retroviruses. And CAV was found in the mitochondria wreaking havoc from what I could ascertain and CFS has major mitochondrial dysfunction.
So unless De Freitas et al made an error and didn't discover an infectious human retrovirus in PWC, we have 2 infectious human retroviruses in patients with Chronic Fatigue Syndrome.
Great overview of that - thanks!
So IF CAV and XMRV are different retroviruses, and I'm not convinced they are, then considering WPI found XMRV active infection in only 67% but antibodies in 95%, could this be because the antibodies for CAV and XMRV are cross reactive? So maybe 2/3 of us have one retrovirus, XMRV, and the rest have the other retrovirus, CAV? This is really getting confusing.
Glad you like it Cort.
Hi CFS Since,
Your clock is perfect for CFS. Time is running away from us and we can never seem to catch up. That's exactly what my clocks in the real world look like to me.
Do you dispute the points that the WPI made about XMRV being different from CAV? I don't know much about virology myself and I'd like to hear more of a discussion about it from those who do.
You bring up a good question. Also, if the JHK retrovirus is 96% similar to XMRV as JerryH pointed out, then are those 2 separate retroviruses and are we showing antibodies to one or the other or both?
Are there any virologists on this list who would care to comment?
I'd also love to hear comments on the statement that CAV (?) were seen (?) associated with (?) : "inside large abnormally distended mitochondria in the cells." Is this common?
We know that mitochondria in CFS aren't working right, that people are profoundly fatigued.
If they are so sure they are different, why don't they put out a press release or at least post something on their website? Putting it as a note on Facebook just seems odd and it is not very well written. I just don't get it. Even if some of their findings are inconsistent with DeFreitas et. al.'s findings it seems to early to say with such conviction that they are different. Presumably technology was very different 20 years ago and maybe DeFreitas was wrong about certain assertions made about the virus size, etc. Maybe this is why it couldn't be replicated. I don't know but as others have said the best way would be either to go back to the samples used in 1991 and test them for XMRV or, if possible, test the XMRV patients for CAV.
Between XMRV and CAV I don't think I can handle trying to figure out how a third virus relates to all this. But I know it is possible to have cross reactive antibodies--to think you have one virus when you actually have a different one. For example this page shows a list of things that can result in false positives for HIV antibodies.
cfs since 1998 that is an amazing list! Goodness.
Well, it seems that doesn't happen often though right? I mean people with HIV have AIDS and those who don't don't. Virologists can actually keep track of how quickly the HIV retrovirus is mutating in each AIDS patient. When you have AIDS you deteriorate quickly without medication and because of its fast mutation rate most patients seem to be constantly changing their meds to try to keep up with it. One patient I saw on tv stated he had already been on 11 out of the 14 HIV drugs available. Our situation appears to be far more muddled than that.
You brought up points that have been mulling around in my head. Just what is the difference between the viral detection technology from 1991 to now? If the WPI and other virologists completely write off and ignore the finding of CAV they're still doing us a disservice. We need testing on CAV done with today's equipment.
Also, good point about how obscurely the WPI announced that CAV is not XMRV. I had to reformat it for myself just to make sense of it. I think that is one of the most important paragraphs I've seen regarding ME/CFS since XMRV was discovered in PWC.
WPI made the following post on their facebook page today:
So, does that mean XMRV was the only virus they were looking for, or the only one they found?
Good question, just because it is the only one they found doesn't mean it is the only one there.
The information being posted on Facebook seems very "unofficial" and possibly interpreted out of context.
Yeah I dunno... I mean this could well be the cause. But it makes you kind of wonder. They hired a virologist and they found a virus. But what if thats not the whole story? Will they look beyond the virus?
Despite everyone screaming "virus" the past 30 years, other things can cause "flu like symptoms". Like pretty much any illness... virus/bacteria/otherwise...
Sorry to sound negative, but it almost seems too perfect.
It was probably written by Andrea Whittemore whos been sick a long time -- she doesnt have a scientific background in any case, I believe.
Be kind of odd to make a press release about it, because it would be natural to scientists to see it isnt the same. DeFreitas' PCR and DNA probes both depend on pretty specific DNA-DNA binding. I am almost sure XMRV's DNA is too different to cross react with HTLV-2 DNA in this way, nor should it cross react serologically. HTLV is not a gammaretrovirus, it is a pretty different varmint.
Heres a BLAST alignment showing that one of DeFreitas' sequences is very different from XMRV. I hope I did this correctly.
This first one is a perfect match to HTLV-II, because DeFreitas took her sequence from known HTLV-II sequences. This match has a one in one billion chance of occurring in a random DNA sequence equally long as HTLV-II's genome. The letters at the bottom show the nucleotides from the query vs the nucleotides of the HTLV-II genome. The little bars are supposed to signify the match of each position, but they are out of alignment because of a change of fonts.
And heres the top match for XMRV, not so great at all. An eleven-nucleotide match this "good" or better has a 0.51 or 51% chance of occurring by chance in *any* random sequence 8200 nucleotides long (the length of XMRV's genome):
> Sorry to sound negative, but it almost seems too perfect.
In science, when things are true, they look perfect or close. If you were buying a used car, "too good to be true" would definitely apply.
Unfortunately, I dont know enough to say for sure whether that 11-nucleotide identity could make DeFreitas' probes or primers bind to XMRV.
If her amplicons are still in the freezer, why the we could sequence em and see if theres any chance she actually amplified XMRV and thought, mistakenly, that it was something close to HTLV-II.
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