CFIDS Report on the 1st XMRV Conference!

pictureofhealth

XMRV - L'Agent du Jour
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Actually this is the clearest summary by far I have read of the First International XMRV Workshop earlier this month - on every level. Certainly much easier to read than the NIH website extracts! Well done to CFIDS for writing this.
Thanks for posting Villagelife - I'm not on Facebook, so its easy to miss some vital info out there from time to time.
 

Berthe

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Great information. But in the report of the CFIDS I couldn't find the name of De Meirleir. If anyone has his posterpresentation or scientific published articles, I would love to have them. Perhaps Frank has them? I start to develop some doubts on De Meirleir and I think I need to be reassured.

Love,
Berthe
 

eric_s

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Good job, CAA, and thanks, Villagelife, for posting. I don't have time to read it now, but i will read it later.

One thing i'm wondering about.. why are the Spanish studies not included in the table comparing the presentations? There are some more positive presentations there.

And what struck my eye in the results of the Hanson/Bell study.. in the "severe" patients the M:F ratio is 2:8 and in the "recovered" patients 6:4. Of course 10 cases is not enough and we don't know how they were selected, but there's a difference.
 

Alexia

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Dr. Yes

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Something confusing here; the CAA report states that the "gag sequences found by Dr. Hanson were more similar to those reported by Lo et al., than to the gag sequences for XMRV, although all are part of the same gammaretrovirus family." However, the abstract describes the gag sequences as XMRV after a BLAST analysis. Either there's a mistake in the abstract, or the CAA got it wrong.

Anyway, I don't think they should contrast "MLV" sequences with XMRV ones; they may just be confused about the terminology, but in case they actually think the viral sequences found by Alter and Lo belong to MLV that have directly infected humans: I think it's most likely that the whole genomes - once sequenced - will prove to be slightly different and will be classified as MLV related viruses; for now it's best to call them "MLV-related sequences". At this stage we don't know for sure whether they all have P-type envelopes (the isolated env fragments were few and small). I would also point out that the distinctions between P and X at the moment are kind of immaterial, until Alter sequences whole virus... even then the most important thing is pathogenic potential, not so much whether they can or cannot infect lab mice.

From the CAA report on Blomberg's talk:

Additionally, he reported finding viral sequences in only 3 of 5 XMRV positive samples received from the WPI.
"Only 3 of 5" is an odd way to spin it.. it's always interesting that the author of a negative study found positives in WPI samples, and even more interesting that they found some positive, but not all - you would expect all to be positive if they were 'contaminated'.

The idea that XMRV might be a passenger virus and that the immunosuppressive state associated with disease might result in the viral infection (rather than the virus possibly causing disease) received some attention. Participants named lessons learned from other retroviruses like gibbon ape retrovirus (prevalent but not disease causing) and HTLV-1 (one agent causing two distinct diseases).
(1) Gibbon ape leukemia virus, as it is correctly called, DOES cause disease in gibbons. The mystery ape expert at the meeting was stupendously wrong.

(2) The example of HTLV-1 was given by Mikovits and others as support for the hypothesis that XMRV causes CFS, not that it is a passenger virus. This point isn't clear at all in the context of this paragraph; it sounds like they're offering HTLV-1 as evidence for the passenger virus idea!
 

Berthe

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Yes dr Yes. Although it was late that evening in Belgium, I also heard Judy M. referring to XMRV causing CFS. If I remember well she said; 'Why would this retrovirus behave/be different than the other retrovirusses already found?!'
 

anciendaze

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(1) Gibbon ape leukemia virus, as it is correctly called, DOES cause disease in gibbons. The mystery ape expert at the meeting was stupendously wrong...
Though I believe the comment was limited to 'neoplasms', I was scratching my head about diagnosing cognitive deficits and fatigue in gibbons found in zoos. I might suggest a psychiatrist to handle the problem.
 

julius

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the distinctions between P and X at the moment are kind of immaterial
at the moment its not known whether it's immaterial or not. It's probably best as we move forward that new researchers and new studies have all available information. Then it will be easier for them to get this all sorted out.
 

Dr. Yes

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Though I believe the comment was limited to 'neoplasms', I was scratching my head about diagnosing cognitive deficits and fatigue in gibbons found in zoos. I might suggest a psychiatrist to handle the problem.
Hey anciendaze,

Do you mean the mystery ape expert was saying there is no neoplasm in Gibbon ape leukemia virus? If so, that would be quite odd, seeing as leukemia is a form of neoplasm. I too would suggest a psychiatrist, but not necessarily for the gibbons... :worried:

at the moment its not known whether it's immaterial or not. It's probably best as we move forward that new researchers and new studies have all available information. Then it will be easier for them to get this all sorted out.
Hi julius,

At the moment the distinction is indeed largely meaningless until, as I said, a genome is fully sequenced (including the env genes) because of the possibility that the virus is a product of one or multiple X-P recombination events. Trying to describe the whole virus as polytropic based on a fragment of the gag gene or env gene is futile; as Coffin pointed out, the results tell us little until the full virus is sequenced. And even if the whole virus is sequenced and it still turns out to most closely resemble a polytropic MLV- what then? Polytropic and xenotropic are just terms for the host range of these viruses in lab mice (not even in most wild mice, which have different receptor alleles), and the difference between the two may be determined by as little as two residues in a single exon of a single gene in the mouse, not so much by the virus itself. The major concerns will be the pathogenic capacity, cell/tissue tropism, infectivity, and insertion sites of the virus. These will depend on sequences other than that which affects its host range; sequences related to pathogenicity include those in the LTR and possibly glycogag regions.

The researchers will of course have all the information, but meanwhile I think some people are placing too much emphasis on categorizing human retroviruses by their host ranges in lab mice. It's not really the P or X designation that matters, but the lineage and corresponding function of the various sequences that make up the virus's genome. And in those respects the distinctions between the two categories blur, due to factors like recombination.
 

julius

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Hey Dr. Oui,

I thought you meant that the fact that they are genetically different was meaningless. I agree that it's not important that it's called X or P. But it is useful to be aware that it is not the single, undifferentiated virus that it was thought to be a year ago.

Given that identifying and finding the virus is still the most confounding aspect of the research, that genetic variability is one of the most important points to consider atm.
 

citybug

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These are the oral and poster presentations on the worksheet. The abstracts are written up elsewhere.

Something confusing here; the CAA report states that the "gag sequences found by Dr. Hanson were more similar to those reported by Lo et al., than to the gag sequences for XMRV, although all are part of the same gammaretrovirus family." However, the abstract describes the gag sequences as XMRV after a BLAST analysis. Either there's a mistake in the abstract, or the CAA got it wrong.
Someone asked him and posted on the CAA facebook page. The abstract was published before the Lo/Alter paper and he didn't feel he should rename the virus, since Murine Related Virus describes it.
 

eric_s

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I think this is interesting, because the way i understand it, it means that other scientists (than the Lo/Alter team) found sequences more similar to those found by Lo et al. than to those found by Lombardi et al. but qualified them as XMRV and did not feel like it's necessary to give them another name.

To me this sounds like the difference between what Lo et al. found and what Mikovits/the WPI found/is finding is not so big, not as significant as some people make it sound.
 

anciendaze

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Hey anciendaze,

Do you mean the mystery ape expert was saying there is no neoplasm in Gibbon ape leukemia virus? If so, that would be quite odd, seeing as leukemia is a form of neoplasm. I too would suggest a psychiatrist, but not necessarily for the gibbons...
I must respectfully disagree, a psychiatrist for the gibbons is essential to enable sound scientific comparison with existing research on humans. Furthermore, recent studies of other infections in wild apes have relied on collecting feces samples and analyzing DNA therein. In the interests of economy, it is clear we can save valuable research money by using a single researcher for all such tasks. Your nominations?

:D
 

Cort

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I think this is interesting, because the way i understand it, it means that other scientists (than the Lo/Alter team) found sequences more similar to those found by Lo et al. than to those found by Lombardi et al. but qualified them as XMRV and did not feel like it's necessary to give them another name.

To me this sounds like the difference between what Lo et al. found and what Mikovits/the WPI found/is finding is not so big, not as significant as some people make it sound.
Its certainly something to get sorted out. Do you know which scientists?
 

Cort

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At the moment the distinction is indeed largely meaningless until, as I said, a genome is fully sequenced (including the env genes) because of the possibility that the virus is a product of one or multiple X-P recombination events. Trying to describe the whole virus as polytropic based on a fragment of the gag gene or env gene is futile; as Coffin pointed out, the results tell us little until the full virus is sequenced. And even if the whole virus is sequenced and it still turns out to most closely resemble a polytropic MLV- what then? Polytropic and xenotropic are just terms for the host range of these viruses in lab mice (not even in most wild mice, which have different receptor alleles), and the difference between the two may be determined by as little as two residues in a single exon of a single gene in the mouse, not so much by the virus itself.
Good points. I think people are just doing what they do - which is try and characterize this one way or the other. We started out with a virus that appeared to be almost homogenous - now we've possibly added a closely related group (but a still distinct group) to the mix. Then we were told they were variants of XMRV. Are they? Or are they pMLV's? I guess we won't know until - as Dr. Yes, points out -they sequence the buggers. XMRV is full of surprises.

The ability to infect different species - in this case the ability to infect humans, is, of course, quite important. pMLV's have not, to my knowledge, proved infectious in humans - a big deal - yet here they are - possibly showing up. (Does this mean they actually are variants of XMRV as Dr. Mikovits has stated?) Its amazing how complex everything gets.

The best I think we can say is that we are - is at the beginning and we'll see how all the genealogies work themselves out over time.

I agree that the key thing is that two closely related retroviruses (or retroviral sequences) appear to have shown up in ME/CFS patients - what an amazing thing that is. :)
 

Dr. Yes

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I must respectfully disagree, a psychiatrist for the gibbons is essential to enable sound scientific comparison with existing research on humans. Furthermore, recent studies of other infections in wild apes have relied on collecting feces samples and analyzing DNA therein. In the interests of economy, it is clear we can save valuable research money by using a single researcher for all such tasks. Your nominations?

:D

He he he. Personally I nominate Drs. Wessely, White or Reeves to talk to the gibbons. Same nominations for the other job, as these men clearly have enormous collections of such samples already.


The ability to infect different species - in this case the ability to infect humans, is, of course, quite important. pMLV's have not, to my knowledge, proved infectious in humans - a big deal - yet here they are - possibly showing up. (Does this mean they actually are variants of XMRV as Dr. Mikovits has stated?) Its amazing how complex everything gets.
In my opinion, there is no significant question that these sequences have shown up; the speculation about contamination is just that - a speculation, and one that cannot explain all the reported results to date. (For more on this see the thread on McClure's contamination argument, as it is dissected in cfssufferer's latest article.)

Both xenotropic and polytropic MLVs would be able to infect other species; many mammals have an Xpr1 receptor that is accessible to both. For some reason, from what I've read so far, no one seems to have looked for MLVs in humans until very recently.