XMRV by Dr. David Bell.
In the CFSAC meeting October 29, Dr. Dan Peterson filled in several blanks. I will present much of what he said at the lecture December 6th. But here is the important piece:
XMRV DNA was found from 68 of 101 patients (67%), and this was in the Science paper. That leaves 33 patients with CFS who were negative. But on further testing 19 of these 33 are XMRV antibody positive, 30 of these 33 had transmissible virus in the plasma, and 10 of these 33 had protein expression. Overall 99 of the 101 patients show evidence of XMRV infection.
These results have interesting implications. The most important is that there is not a simple test now that will tell you if you have XMRV or if the virus is active in your system. And we need a good control study using all three measures to accurately know control presence of the virus. This is not a fly-by-night operation. Right now, it is necessary to do several tests to know the XMRV status:
a) DNA by PCR
b) Viral infectivity
c) Detection of viral proteins
d) Antibody to the XMRV envelope
As time goes on and we learn more, this process will be simplified. What I do not want is poor science that will cast doubts on an illness that already has its fill of doubters. Let’s do it right from the beginning. If by doing it right XMRV proves not to be the cause, so be it. Something is the cause.
Dr. Coffin of Tufts University and the National Cancer Institute presented some very interesting observations. He is a true veteran (45 years) of retroviral research. There have been comments from various people saying that there are lots of viruses associated with CFS, so what is the big deal? Among the points raised by Dr. Coffin:
A) it is relatively difficult to isolate live retrovirus from patients with HIV infection, but relatively easy to isolate live XMRV in CFS. There is a high percentage of infected cells.
B) The percentage of positive controls for XMRV not that much different between CFS controls and prostate cancer controls, 4 or 5%. However, much work needs to be done to verify the control incidence. This is particularly true because the nations' blood supply could be contaminated. (By the way, no patient with ME/CFS should donate blood - personal opinion) The Japanese Red Cross has said that there is a "low incidence" of XMRV in their blood supply.
C) Could some mouse have contaminated the tests by shedding some XMRV in the lab? XMRV is a big family of "simple" retroviruses. In the XMRV strains isolated in CFS patients there is a 0.3% diversity from what are carried in mice - a relatively large diversity. This virus does not vary with replication as much as HIV does. In two weeks of HIV replication the diversity is greater than 0.3%. And this is both good and bad news. Good news for the ultimate production of a vaccine. The diversity has been a roadblock in the production of a HIV vaccine. Bad news for the antiviral therapy implications. But that is way down the road.
D) Dr. Coffin presented a slide of the many things we do not know about XMRV. There are lots of things to do.
E) Dr. Coffin mentioned that there is excitement in the retroviral scientific community - very good news for the ME/CFS community. We will get confirmation, or lack of confirmation, from many good scientists. It will be difficult for biased scientists to squelch this, if it is, in fact, true.
The statement that made my socks roll up and down all by themselves was a reply to a question from the committee. Dr. Coffin said "This was as good as it gets for a first paper, but it is still just a first paper."
Theory of Mechanism of XMRV and ME/CFS
Dr. Peterson presented an update of a theory of mechanism that has been circulating for many years. Ironically enough, it was once called the "X factor theory."
Step 1: Infection with XMRV. No idea of how this happens. Could it be that the tiny XMRV piggybacks onto some huge, lumbering herpes virus like EBV, or HHV6. That mechanism is known to occur. Lots of other possibilities
Step 2: Infection of B, T lymphocytes and NK cells. Dr. Klimas has said that up to 70% of lymphocytes are "activated". Something is going on.
Step 3: Impairment of NK cell number and activity. Because of the retroviral infection, the NK cells are impaired. This is parallel to what is known to happen in HIV disease with the CD4 lymphocytes
As a result of poor NK cell and function (and other T & B cell problems) the person now has an immunodeficiency. NK cells are important in the control of herpes viruses and other agents.
Step 4: Reactivation of other agents. Increased viral load of EBV and other agents cause cytokine production, activation of 2'-5'A Synthetase, RNAse L which contribute to symptoms. It is interesting to note that AIDS patients feel better with suppression of secondary infections. This could explain why treatment with antibiotics, antivirals, gamma globulin and other agents make some patients with ME/CFS feel better for a while.
Archived video of Dr. Daniel Peterson's presentation of the CFSAC 10/29/09 should be available at: http://videocast.nih.gov/PastEvents.asp
. It is my personal opinion that it is history in the making. Time will tell.
And while I am making rash predictions, let’s talk about the name of this illness. It has been a favourite topic of mine since the "Disease of a Thousand Names." Chronic fatigue syndrome is a miserable name. I think that XMRV is going to turn out to be the puppet-master that pulls the strings of illnesses variously called CFS, ME, fibromyalgia, atypical multiple sclerosis, chronic mononucleosis…. And if it does, the name should be XAND, for Xmrv Associated Neuroimmune Disease. I heard Mrs. Annette Whittemore use this term and it feels right. History.