Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome
Vincent C. Lombardi,1* Francis W. Ruscetti,2* Jaydip Das Gupta,3 Max A. Pfost,1 Kathryn S. Hagen,1 Daniel L. Peterson,1 Sandra K. Ruscetti,4 Rachel K. Bagni,5 Cari Petrow-Sadowski,6 Bert Gold,2 Michael Dean,2 Robert H. Silverman,3 Judy A. Mikovits1† - 8 October 2009

Innate Immune Changes in the Peripheral Blood of Chronic Fatigue Syndrome Patients: Risk Factors for Disease Progression and Management (pp. 91-130) $0.00

Authors:  (Deborah L.S Goetz, Judy A. Mikovits, Jamie Deckoff-Jones, Francis W. Ruscetti, LANDRES Management Consultant, MAR Consulting Inc., Private CFS Practice, and others)
Chronic Fatigue Syndrome (CFS) is recognized by the WHO as an alternative name for Myalgic Encephalomyelitis, which has been classified as a disease of the central 
nervous system since 1969. The concept that chronic microbial infection drives constant activation of the innate immune system through alterations in the production of innate 
immune cells and accompanied by abnormal production of pro-inflammatory cytokines and chemokines, and that this leads to progressive immune deficiency seen in many CFS 
patients has only recently been appreciated. In investigating the distribution of immune cells in the peripheral blood of a cohort of CFS patients who have an antibody 
recognizing the SFFV envelope protein, we discovered profound alterations in the number and types of cells, particularly in the cells regulating the innate immune system. 
These changes included chronic activation of monocytes and dendritic cells, and a marked increase in NKT cells and decrease in NK cells. The cytokines in plasma from 
these CFS patients was assayed in a multiplex platform, and one of us published findings showing signatures of infection; that is, significantly high levels of many proinflammatory 
mediators such as IL-12, MCP-1, IL-8, IP-10, IL-6, TNF-α, and IL-1β while being low in the critical antiviral cytokine IFN-α. In expanding these results, we 
found that subsets of these CFS patients had increased TGF-β and others had increased IL-9. We will discuss these and other published results that suggest that chronic stimulation of the innate immune system is a component of the development and progression of disease in many CFS patients. In chronic diseases the resulting immunodeficiency allows activation and replication of many secondary pathogens. Thus CFS patients can share complex pathogenic complications with patients with HIV AIDS and HTLV-1 associated myelopathy. In many CFS patient populations, the presence of several concomitant infections, from Borrelia burgdorferi to reactivated exogenous and endogenous viruses, chronically dysregulating the immune system, is a major risk factor in the development of pathology. Other risk factors include alterations in microbiota regulation, mitochondrial toxicity, cognitive dysfunction and impaired methylation pathways. These factors can also increase the risk of others diseases, including cancer, in some CFS patients. These results have important implications for the management of many people with this diagnosis. We will review in this chapter the use of antiinflammatories, anti-virals and other therapies, as well as discussing how repurposing drugs holds promise in the treatment of patients displaying the immune abnormalities identified in these CFS patients.    Click the pdf at the bottom of the page to see the whole chapter.

The Exotic Biology of Xenotropic Murine Leukemia Related Viruses: Pitfalls and New Concepts - This presentation from Dr. Judy A. Mikovits at the Mount Sinai Conference in November of 2013 details the very latest findings on the exotic biology of the murine leukemia retroviruses and the role they may play in many human diseases. (44 slides):

Papers & References

Seroconversion assays for detecting xenotropic murine leukemia virus-related virus
US 20100167268 A1
Methods of detecting, diagnosing, monitoring or managing an XMRV-related disease such as an XMRV-related neuroimmune disease such as chronic fatigue syndrome or an XMRV-related lymphoma such as mantle cell lymphoma in a subject are disclosed. These methods comprise determining presence, absence or quantity of antibodies against XMRV in a sample from a subject.

Publication number US20100167268 A1
Publication type Application
Application number US 12/575,467
Publication date Jul 1, 2010
Filing date Oct 7, 2009
Priority date Jul 15, 2009
Inventors Judy A. Mikovits, Francis W. Ruscetti, Sandra K. Ruscetti
Original Assignee Mikovits Judy A, Ruscetti Francis W, Ruscetti Sandra K

Epigenetic Control During Limphoid Development and Immune Responses - Aberrant Regulation, Viruses, and  Cancer - 2003

Kathrin Muegg, Howard Young, Francis Ruscetti, and Judy Mikovits

Patent-Combination therapy for prostate cancer using botanical compositions and bicalutamide 
WO 2012061790 A1

Suramin and Purinergic regulation papers 

Using a cytokine signature to diagnose disease or infection 
WO 2012106674 A3
Provided are methods and compositions for detection of levels, activity, or expression of cytokines so as to determine a cytokine signature. A cytokine signature of a subject can be compared to a control or reference value(s) and differences there between used in the diagnosis or monitoring of a neuroimmune disease or a retroviral infection.
Judy A. Mikovits

Xenotropic Murine Leukemia Virus-related Virus-associated Chronic Fatigue Syndrome Reveals a Distinct Inflammatory Signature – (The cytokine signature paper was published in 2010 and first presented in CFS patients at IiME in London in 2008). This research by Dr. Judy A. Mikovits, was the first to identify a signature of 10 cytokines and chemokines which would correctly identify XMRV/CFS patients with a 93% specificity and 96% sensitivity.

Purinergic signalling and the autonomic nervous system in health and disease Click here to read paper

Stretch-activated calcium channel protein TRPC1 is correlated with the different degrees of the dystrophic phenotype in mdx mice

Purinergic regulation of the immune system

P2X7 Receptor Antagonists Display Agonist-like Effects on Cell Signaling Proteins

P2Y6 receptors are involved in mediating the effect of inactivated avian influenza virus H5N1 on IL-6 & CXCL8 mRNA expression in respiratory epithelium

Sensory input to the central nervous system from the lungs and airways: A prominent role for purinergic signalling via P2X2/3 receptors

Purinergic Signaling in the Airways

Identification, Viral Dissemination and Antibody Responses of Rhesus Macaques Exposed to the Human Gammaretrovirus XMRV – This research from Emory University showed that murine leukemia viruses tend to disappear quickly from the blood, settling in specific organs, but can easily be reactivated by immune stimulation.

Frequent Detection of Infectious Xenotropic Murine Leukemia Virus (XMLV) in Human Cultures Established from Mouse Xenografts - This chilling research from the well-regarded Dr. Adi Gazdar, suggests that the murine leukemia retroviruses may have the potential to become airborne.  In their conclusion the Gazdar team warned, “Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially bio-hazardous human-tropic mouse viruses and their spread to other cultures.”