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Thanks for posting that. I believe there is a another trial going on targeting HERV activation in MS, with a different agent (there should be a thread on here somewhere...)</p>
<p> </p>
<p>also this by some of the researchers involved in the trial:</p>
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<p><span style="font-size: x-large"><span style="font-weight: bold"><span style="font-size: medium"><a href="
http://msj.sagepub.com/content/18/12/1670.full" target="_blank" class="externalLink" rel="nofollow">HERVs: have we been here before?</a></span></span></span>
The research that Miller and I were engaged in dealt with the possible neurological damage caused by XMRV when XMRV was available as viable candidate for ME/CFS research prior to the controversial negative papers. The patient involvement or aspect got scrapped after contamination but the research continued and was researched. It was released in Feb. 2012.
Journal of Virology
J Virol. 2012 February; 86(3): 1661–1669.
doi: 10.1128/JVI.06073-11
PMCID: PMC3264382
Xpr1 Is an Atypical G-Protein-Coupled Receptor That Mediates Xenotropic and Polytropic Murine Retrovirus Neurotoxicity
Andrew E. Vaughan,a Ramon Mendoza,a Ramona Aranda,a,* Jean-Luc Battini,b and A. Dusty Miller
Note:
The bolded part is a bit down toward the end of the paper
.....While it seems clear now that XMRV is not associated with CFS, our study provides unique insights into a potential role for Xpr1 in neural biology. A role for deregulated cAMP signaling has clear precedents in other disease models and developmental observations. ......However, neuropathology can also be found in mice following infection by some ecotropic retroviruses, such as CasBr-E MLV, that do not use Xpr1 as a receptor. Our studies show that CREB is activated by Xpr1 signaling because CREB is the transcription factor that drives SEAP expression in the assay that we employed to measure cAMP levels. In addition, cAMP-modulating drugs have been shown to reverse neurodegeneration in cultured hippocampal neurons treated with amyloid β-peptide, a model of Alzheimer's disease.
Our studies show that CREB is activated by Xpr1 signaling because CREB is the transcription factor that drives SEAP expression in the assay that we employed to measure cAMP levels. In addition, cAMP-modulating drugs have been shown to reverse neurodegeneration in cultured hippocampal neurons treated with amyloid β-peptide, a model of Alzheimer's disease. Moreover, mice infected with multiple neuropathic polytropic MLVs displayed increased expression levels of proinflammatory cytokines and chemokines, and neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis induce similar cytokine and chemokine expressions.
Xpr1 is involved in normal brain function. Notably, neuropathology can be induced in mice following infection with various retroviruses, and some studies have shown that polytropic retroviruses are neuropathic, while related ecotropic retroviruses that do not use Xpr1 as a receptor are not. However, neuropathology can also be found in mice following infection by some ecotropic retroviruses, such as CasBr-E MLV, that do not use Xpr1 as a receptor. The infection of mice with ecotropic retroviruses frequently results in recombination events leading to the production of polytropic retroviruses and it would be interesting to determine if these recombinant viruses play a role in neurologic diseases induced by ecotropic retroviruses.
Also
Autoimmune disease: A role for new anti-viral therapies?
Source
Pediatrics, Yale University School of Medicine, New Haven, CT, United States.
dhdreyfus@pol.net
Abstract
Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and autoimmune diseases.
Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism.
Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk.
Copyright © 2011 Elsevier B.V. All rights reserved.
ALSO
Clin Exp Immunol. 2013 May 9. doi: 10.1111/cei.12133. [Epub ahead of print]
Flow Cytometric Assay Detecting Cytotoxicity against Human Endogenous Retrovirus Antigens Expressed on Cultured Multiple Sclerosis Cells.
Source
Department of Biomedicine, Bartholin Building, Wilhelm Meyers Allé 4, Aarhus University, DK-8000 Aarhus C, Denmark.
Abstract
Damage of target cells by cytotoxicity, either mediated by specific lymphocytes or via antibody-dependent reactions, may play a decisive role in causing the CNS lesions seen in Multiple Sclerosis. Relevant epitopes, antibodies towards these epitopes, and a reliable assay are all mandatory parts in detection and evaluation of the pertinence of such cytotoxicity reactions. We have adapted a flow cytometry assay detecting CD107a expression on the surface of cytotoxic effector cells to be applicable for analyses of the effect on target cells from MS patients expressing increased amounts of human endogenous retrovirus antigens. MS patients also have increased antibody levels to these antigens.
The target cells are spontaneously growing PBMCs of B-cell lineage, expressing HERV epitopes on their surface. Polyclonal antibodies against defined peptides in the Env- and Gag-regions of the HERVs were raised in rabbits and used in ADCC-assays. Rituximab®(Roche) a chimeric monoclonal antibody against CD20, primarily expressed on B cells, was used as control antibody. Without antibodies this system is suitable for analyses of NK activity.
In optimization of the assay we have used effector lymphocytes from healthy donors. The most effective effector cells are CD56+ cells. CD8+ T-cells also express CD107a in ADCC. Using the adapted assay we demonstrate significant ADCC activity to target cells expressing HERV epitopes, and additionally a low level of NK activity.
This article is protected by copyright. All rights reserved.
ALSO
Multiple sclerosis: autoimmunity and viruses.
Source
Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
Abstract
PURPOSE OF REVIEW:
This review will explore two new aspects of the involvement of viruses in multiple sclerosis pathogenesis. The first aspect is the complex interactions between viruses. The second aspect is the proposal of a mechanism by which autoreactive T cells are able to escape thymic selection and potentially recognize self and a pathogen.
RECENT FINDINGS:
With regard to viruses, recent work has demonstrated that one virus may enhance the replication of another virus, potentially leading to an increase in inflammation and disease progression. Also, interactions between human endogenous retroviruses, which likely do not replicate, and certain herpes viruses, may also play a role in disease pathogenesis. Mechanistically, T cells expressing dual T-cell receptors would be able to recognize self and a foreign antigen specifically. Therefore, human endogenous retroviruses potentially play a role in multiple sclerosis pathogenesis, and both interactions between multiple viruses and autoreactive CD8 T cells with dual T-cell receptors may play a role in the pathogenesis of the disease.
SUMMARY:
The complex interactions between multiple viral infections, either within the central nervous system or in the periphery, and the host immune response to viral infection may be such that a variety of viral specificities result in the activation of T cells that recognize self and induce multiple sclerosis. Therefore, it is unlikely that any one microbe will be determined to be the causative agent of multiple sclerosis as reflected by the number of potential triggering mechanisms of the disease.
PMID:
23656710
[PubMed - as supplied by publisher]
My Comment:
This means that other fields of research are investigating other possible causes of their illnesses which have a pathogenic etiology and using other treatment options for their patients base on their own research which could be a potential benefit for the ME/CFS community. It lends credence to the fact that if other researchers are allowed a trial treatment program for their patients based on similar etiology (EBV - Herpes Viruses or possible HERV) than why shouldn't the ME/CFS researchers be allowed to have a similar trial for their patient community. It begs the question. I know of two doctors who have benefited from this type of treatment protocol.
Eco
