Dr. Cheney on XMRV Workshop

[Guest guest]

From MEActionUK group- " Rich Van Konynenburg has posted this to

a few groups tonight. Permission to re-post as long as Dr Cheney is

acknowledged. "

MEActionUK/message/63373

==============================================

From Dr Cheney

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 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.

Cheney, M.D.