1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Ergonomics and ME/CFS: Have You Hurt Yourself Without Knowing It?
Having a chronic illness like ME/CFS can make it hard to avoid problems that come from bad ergonomics. Jody Smith has learned some lessons the hard way ...
Discuss the article on the Forums.

Dr. Cheney comments on the XMRV workshop

Discussion in 'XMRV Research and Replication Studies' started by richvank, Sep 10, 2010.

  1. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    747
    Hi, all.

    Dr. Paul Cheney has given me permission to post the following comments that he has written about the XMRV workshop on Sept. 7-8, 2010, which he attended. Please don't address questions to me about his comments, because I do not want to keep bugging him. I hope you will understand.

    Best regards,

    Rich


    "I attended and was a poster presenter at the recently completed XMRV conference at the NIH. It was fascinating and I took perhaps 30 pages of notes. The bio-political undertones were also intense but I have to say that the presentations of XMRV association with CFS (4 presentations) were much stronger than the presentations of negative XMRV associations with CFS (4 presentations). They were stronger specifically because of the multiple methods they employed and not just PCR. Very interesting in this regard were comments by the head of the blood working group at the NIH who is trying to determine the cause of the discrepancy. He hinted strongly that it is the way blood is collected and processed for nucleic acids and not the detection methods for XMRV itself that divides the two groups. In an NIH blood group sponsored study, a group comparison study with both camps represented detect successfully, in a blinded fashion, XMRV spiked buffer in varying concentrations but they nevertheless divide into two camps when clinical blood samples are taken and processed for XMRV nucleic acids. Using only PCR, one camp sees ~80% positive in CFS and one camp sees 0% positive in CFS There is no one in between and no middle ground between the two groups which was striking and noted by Joe B. who was also in attendance. There is no evidence by mouse mitochondrial DNA probes, that any of the positive associations were contaminated. However, one of the negative association speakers found non-human mouse virus MLV contamination perhaps localized to heparin tubes used for blood collection. Heparin is often produced in China where mice are common as pets. When the contamination was cleared, she found no association of XMRV with CFS.

    "I also wanted to share some other highlights of the conference Among them, a very interesting presentation was made by a group connected to Abbott Labs that infected male and female Macaques (monkeys closely related to man) with human XMRV to see what happens and where the virus ends up or concentrates itself.

    "Within a few weeks, the virus was largely cleared from blood where it was initially injected in high concentration. Even antibody response was lost over time (months) as the infection was largely removed from the blood and virus did not appear to persist in the blood. Apparently, there was not enough viral antigen to keep antibody levels high or persistent. However, the virus was found more or less in every organ, at least initially, and thought to be carried around the body in T-cells and B-cells during the active phase of infection. This is consistent with the ubiquitous nature of the Xpr1 receptor used by the virus to gain access to almost all cells of the body. Organs where the virus was initially most concentrated appeared to be lymphoid organs such as the spleen, liver and mesenteric nodes of the GI track and in sex organs and in particular the epithelium of the prostate gland where it was highly concentrated at first and then the infected cells later apoptosed and infection disappeared from the epithelium and then the virus was more likely to be seen in the interstitial cells in the stroma or matrix of the prostate, especially the fibroblasts which may be one reservoir in all the various organs that are initially infected. The virus was also found in the epithelium of the cervix in the female macaque. Over time, the infections of various organs tended to be cleared by either immune mechanisms but especially by restriction enzyme systems present in almost all human cells that hypermutate the virus so it cannot persist as a competent infectious agent. Indeed, mutated viral strains are almost always found in CFS cases by both Judy Mikovits at WPI and Frank Ruscetti at NCI. Sometimes this makes the virus incompetent as an infectious agent and sometimes has no effect on infectiousness.

    "Very interesting is that another cell that appears to be a reservoir of XMRV other then fibroblasts within tissue stroma are tissue macrophages The pulmonary alveolar macrophages were absolutely loaded with XMRV virus and other tissue macrophages could also be a potential reservoir in other tissues as well, especially in the GI tract, sex organs and sinuses. Tissue macrophage reservoirs would be analogous with HIV as well. It would seem that bronchial secretions, nasal secretions and sex organ secretions as well as feces and urine are well positioned to help the virus to spread itself to other macaques, especially if activated.

    "As for activation of more or less low level or quiescent but persistent infectious virus, there seem to be several mechanisms. The virus has both a glucocorticoid response element (GRE) and an androgen response element (ARE) in its promotor region. It also has binding regions for NK Kappa B proteins in its response elements. In any organ with high levels of local androgenic stimulation such as the prostate and perhaps during puberty, the virus could activate. No mention was made of the effect of the predominant female sex hormones but estrogen is the equivalent androgen-like hormone in females. As for the GRE in the promotor region, severe stress will activate the virus or the use of glucocortocoid hormones and perhaps any precursor steroid hormone such as pregnenolone. As for the NF Kappa B sites, any strong immune response with an associated cytokine storm would also be a strong stimulant and such stimulation certainly occurs in the bronchial tree which is frequently stimulated with antigen, especially during allergy season.

    "Perhaps most interesting of all was what happened with the injection of a bolus of foreign peptides into macaques that had apparently completely cleared the virus from blood. There was a huge reactivation of infectious virus in the blood proving that latent but persistent virus is just below the surface and that XMRV infection cannot be completely cleared from all reservoir sites. The peptide injection mimics an acute infection (? borrelia or the flu), an immunization or even acute mold exposure.

    "The effect of XMRV infection over time was not studied in the macaque but a similar gammaretrovirus called Feline Leukemia virus (FeLV) has been well studied in cats for decades. I will in another post describe a most interesting talk at this conference by a veterinarian on the life history of infection by a gammaretrovirus in cats."

    Paul Cheney, M.D.
  2. Sasha

    Sasha Fine, thank you

    Messages:
    8,065
    Likes:
    6,869
    UK
    Wow! Thanks, Rich - v. interesting about the differences between the methods of the +ve and -ve studies.

    The rest is a bit over my head - can anyone provide a simple summary in just a few sentences about what Dr Cheney is saying about the virus starting off in the blood and then...? Just the big picture?
  3. LaurelW

    LaurelW Senior Member

    Messages:
    552
    Likes:
    92
    Utah
    Thanks, Rich. That's really interesting.
  4. ukxmrv

    ukxmrv Senior Member

    Messages:
    3,445
    Likes:
    1,946
    London
    Thanks Rich, Is it OK to repost this as long as people know not to bug you (to bug him)?
  5. aquariusgirl

    aquariusgirl Senior Member

    Messages:
    947
    Likes:
    91
    yep, fascinating, thanks rich
  6. George

    George waitin' fer rabbits

    Messages:
    846
    Likes:
    44
    South Texas
    Thanks Rich you are my hero! Big kisses to you and Dr. Cheney.
  7. pictureofhealth

    pictureofhealth XMRV - L'Agent du Jour

    Messages:
    534
    Likes:
    1
    Europe
    Absolutely fascinating and great to finally get a comprehensive picture of some of the research from the inside. Thank you Rich and to Dr Cheney.

    Everything described about the way in which XMRV replicates and hides out in the body and resurfaces makes total sense. No wonder it is such a difficult illness to overcome - the virus seems to have an advantage from all angles!

    I am so grateful to Dr Mikovits, the Ruscettis, the WPI and all the research teams for their hard work, insights and tenacity so far. Also to the monkeys - risky comment, but seriously! Am so looking forward to seeing the published papers. Thank you.
  8. jimbob

    jimbob ME/CFS84-XMRV+

    Messages:
    321
    Likes:
    9
    myrtle beach, s.c.
    Thanks rich, Cheney is a pretty smart hombre, no!
  9. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    747
    Hi, uksmrv.

    Yes, it's fine to repost it, and please do attribute it to Dr. Cheney.

    Best regards,

    Rich
  10. mojoey

    mojoey Senior Member

    Messages:
    1,097
    Likes:
    59
    This is the takeaway I got from it:

  11. Snickers

    Snickers

    Messages:
    13
    Likes:
    0
    Virginia, USA
    Hmm...so from this study it sounds like XMRV may only be a problem when other infections are present and reactivate it? Isn't that along the lines of what some other people here mentioned on the McClure thread? Here is one quote from that thread...

  12. Sasha

    Sasha Fine, thank you

    Messages:
    8,065
    Likes:
    6,869
    UK
    But then it gets reactivated? Or something? :confused::confused::confused:
  13. mentalist

    mentalist

    Messages:
    7
    Likes:
    0
    This is Dr. Cheney's quote:

    However, the virus was found more or less in every organ, at least initially, and thought to be carried around the body in T-cells and B-cells during the active phase of infection. This is consistent with the ubiquitous nature of the Xpr1 receptor used by the virus to gain access to almost all cells of the body.

    He said nothing about ubiquitousness of the virus, only receptor.
  14. dannybex

    dannybex Senior Member

    Messages:
    2,177
    Likes:
    518
    Seattle
    Joey...can you translate into laymen's terms -- for those of us who are scientifically challenged -- what this means? For example, what are "restriction enzyme systems"?
  15. Sasha

    Sasha Fine, thank you

    Messages:
    8,065
    Likes:
    6,869
    UK
    Wish I'd done biology... :confused:... wish I'd done biology...:confused:
  16. mojoey

    mojoey Senior Member

    Messages:
    1,097
    Likes:
    59
    Hey Danny,

    Frankly this is new to me too!! I was just taken by the hypermutation aspect because we've been hearing a lot about drugs that hypermutate HIV out of existence (I posted some of these on my thread: http://www.forums.aboutmecfs.org/showthread.php?7403-Eradicating-reservoirs-of-HGRV&p=121789#post121789

    According to wikipedia:

  17. dannybex

    dannybex Senior Member

    Messages:
    2,177
    Likes:
    518
    Seattle
    Thanks Joey -- this is all so complex and fascinating -- and frustrating! -- but I'll continue to follow on the other thread. Lisa has asked some interesting questions over there...
  18. urbantravels

    urbantravels disjecta membra

    Messages:
    1,333
    Likes:
    506
    Los Angeles, CA
    Utterly fascinating! Thanks for sharing, richvank.

    The FeLV connection also sounds interesting...look forward to reading that too.
  19. VillageLife

    VillageLife Senior Member

    Messages:
    674
    Likes:
    36
    United Kingdom
    wow!!! !!!!!!
  20. bullybeef

    bullybeef Senior Member

    Messages:
    476
    Likes:
    44
    North West, England, UK
    Very well done for getting that response. So much there to chew the fat off!!

See more popular forum discussions.

Share This Page