XMRV

Current testing, primarily by VIP Dx in Reno, gives three results. 1) Serum RT-PCR for viral RNA 2) Whole blood PCR for viral DNA and 3) Culture of human blood white cells which amplifies the infection to see it better and the most sensitive of the three tests, the most labor intensive and the most costly. Coming soon will be antibody testing including 4) IgG against common viral proteins and 5) Western blot (WB) which looks at the entire pattern of viral protein antibody expression which are present and considered the gold standard for confirming any direct detection of virus by PCR or RT-PCR testing which is subject to false positives. When IgG ELISA testing is available, there will likely be a contraction of standard testing to just serum RT-PCR and whole blood PCR and IgG if positive to confirm and perhaps IgG if negative to confirm any past infection which, of course in a retrovirus, is permanent infection of your DNA. There are other issues involving infectiousness and viral latency that are peculiar to retroviruses. Below is a fuller explanation.

I have observed ventilatory and echocardiographic responses to 4 lpm NC oxygen every day in this practice for over three years now, admittedly in a rarified group of long time ill (ave 15 years) and very disabled (ave KPS of 50-60) cases of well characterized CFS cases. They have large ventilatory reactions (hyperventilatory and hypoventilatory) and some express immediate dislike of oxygen and get very anxious and agitated. A few have stopped breathing and had to be noxiously stimulated to revive them off oxygen. The echo shows an average of 10-20% loss of free energy by IVRT criteria on 4 lpm NC oxygen which means decreased ability to pump calcium out of the myocardium and relax and fill properly the LV. This cannot be a good thing if sustained and has potentially deeper threats related to poor oxygen handling such as DNA damage from accelerated ROS.

A recent publication out of Germany (Hohn O. et al, Retrovirology, 2009 Oct 16;6(1):92. [Epub ahead of print] – PMID: 19835577) reports that prostate cancer patients with a known RNAse-L mutation, linked in the US to XMRV, had no evidence of XMRV infection. The same type of patient was shown to be associated with a high incidence of XMRV infection reported by the Cleveland Clinic in 2007.

It is my sense that infectious RV’s and possibly Herpes Group viruses are universal “test” agents for cells they infect to see if they can buffer their redox state in the case of either an externally induced redox shift to a more oxidizing environment or internally produced by the viruses themselves as they have the machinery to do it. If they can overwhelm the redox buffer, they replicate rapidly and kill the cells which lytically explode releasing virions to try again in other cells. If you cannot control the redox buffer systemically, you die because such loss of buffer threatens the DNA and the species with it. Therefore, these endogenous viruses are the wolves culling out the weak sheep in the flock of humans who in turn face external environmental challenges that threaten their redox balance. By this method, these endogenous viruses and especially RV’s direct human evolution to some unknown end but they only allow the subset of humans who can properly defend their redox state to survive or procreate.

As for other immune aberrations, they abound in CFS and the literature is full of them. CFS is an immune activation state involving both innate and cognate immunity and it is quite easy to show something immunologically abnormal in any of these patients. The problem is non-specificity of these immune aberrations and the fact that they come and go over time as these patients evolve and adapt immunologically. The co-infections and co-morbidities also make this a real immunologic nightmare for high-specificity correlations to XMRV. Perhaps someone will come up with an immune marker for XMRV that is both sensitive and specific now that it is in our sights. However, even low CD4 is not sensitive and specific to HIV infection. CD4 is more sensitive to HIV-AIDS evolution but even here there is not complete specificity as NIAID has a non-HIV AIDS clinic with low CD4 counts filled with CFS.

The possible presence of XMRV, especially if it resides in the brain which is very likely, could be activated by an immune activation state produced by immunotoxins such as VOC’s as well as influenza vaccines.

There are ways that retroviruses can impact the cell the I believe are especially important to CFS and data exists to support these assertions both in the literature (see below) and in such findings as low SOD and GPx in CFS and provides a mechanism to explain oxygen toxicity by ETM which is nearly universal in CFS.

As for overlap conditions in Dr. Mikovits’ cohort associated with CFS including FM and MCS and chronic Lyme and MS-like patients, I cannot speak to that. However, my clinic is filled with such overlap conditions. I suspect it will not matter very much. They are most likely infected with XMRV if they meet criteria for CFS with or without FM or MCS or chronic Lyme. Perhaps pure FM or pure MCS or pure Lyme will be different in degree of infection and maybe not. It will be very interesting to watch this data develop and expand to CFS-like conditions and the few pure FM and MCS cases that I have seen over the years. I have not really seen what I would call a pure Lyme case but many with CFS and a positive Igenex WB assay and antibiotic failure for chronic Lyme.

Proper buffering of the redox set point for the human body’s biological terrain is critical to control intracellular viral replication. Oxidative stess will potentially amplify XMRV replication. The biggest amplifier of oxidative stress due to any cause is NF Kappa B and one of the best inhibitors of NF-kB are the artemisins (Artesunate and Wormwood). Artemisins are also thought to be useful in cancer. We will be exploring the dose response curve for Artemisins to inhibit infectious XMRV in the near future to determine the best dose. We already know that activating NF-kB activates this virus and suppressing NF-kB inhibits XMRV. Artesunate is also known to inhibit HIV and all the associated herpes viruses that are co-factors in the evolution of AIDS and CFS as well.

The finding of antibody or active virus in 95% of CFS and 4% of controls is a result that argues for causality, in my opinion, especially with the associated RNAse-L corruption and NK functional impairment that might predict such an infection. This novel retrovirus could easily shift the redox state just like HIV as has been published in (2001) and (1995) and induce all manner of associated pathogens as seen in CFS. A redox shift could ultimately corrupt the gut ecology and create P450 decoupling based on NADPH depletion observed in CFS and lead to environmental illness as well. Time will tell but I think Dr. Mikovits is right to suspect causality. I also think this virus is infectious with at least ten million Americans infected who appear healthy and perhaps another four million Americans or more with CFS as recently estimated by the CDC (2007). However, disease expression may be more limited causing the illusion that it is not infectious. Furthermore, there may be other diseases that are similar and dissimilar to CFS that are associated with if not caused by XMRV.