Journal of IiME Volume 7 Issue 1 neurological dysfunction in GWI. GWI affects 25-30% of the one million military personnel who served in the 1991 Persian Gulf War. Veterans with GWI present with multifaceted symptom profiles similar to ME/CFS patients. In fact, overlap in symptoms often leads to co-morbid diagnosis. The data presented today provides the first direct evidence of i) white matter damage that is associated with the complaints of pain and fatigue ii) elucidation of two phenotypes in response to exercise stressors iii) neurological evidence of compensatory cognitive function iv) cortical, cerebellar, and brainstem damage associated with exercise induced phenotypes and v) cognitive alterations associated with abnormal energetics of lactate metabolism in the prefrontal cortex possibly linked to neuronal mitochondrial dysfunction. An important confounder is the use of different designation criteria to diagnose patients. This has created difficulties for clinicians to identify cases and also hindered meaningful collaboration between researchers. Current phenomenological case definitions have considerable consistency and functional overlap. What is clear is the need to shift focus from aetiology and "symptoms at rest" to the response of the CNS to physiological perturbations. Although heterogeneity in symptom complexes exists; it may be too subtle to elucidate true subphenotypes at baseline. This is due to the remarkable ability of the brain to recover function and hide the underlying insult. Pushing the CNS beyond its compensatory capabilities removes the phenotype dependent functional stopgap and leads to unchecked pathophysiological profiles that amplify subgroups that would otherwise go unnoticed. We propose that fMRI of patients before and after stressor protocols may provide the distinct advantage of a standardized top-down approach that will lead to biomarker discovery of subphenotypes, individual pathophysiology, and tailored therapies. Retroviruses and ME Professor Greg Towers Professor of Molecular Virology, Research Department of Infection, Div of Infection & Immunity, University College London, UK Research Activities: HIV,Host factors influencing viral tropism and antiviral innate immunity, Innate Invest in ME (Charity Nr. 1114035) (May 2013) Immunity, Retrovirus in gene therapy and xenotransplantation, Transcription and chromatin Abstract Greg J Towers and Stephane Hue Infection and Immunity, University College London Why do we think that XMRV is not a human pathogen? Xenotropic murine leukaemia virus related virus (XMRV) is a mouse gammaretrovirus. In 2006 XMRV was described as being present in prostate cancer samples using a new technique of virus discovery. Several labs began to study the association between XMRV and human disease. In 2009 XMRV was associated with samples from patients with ME/Chronic Fatigue. This study raised particular interest because it also found XMRV in samples from healthy controls suggesting that XMRV may be a new human pathogen infecting millions of individuals. Our interest in studying the life cycle of retroviruses led us to consider whether XMRV was truly a human pathogen. We found that patient derived XMRV sequences were almost identical to a mouse xenotropic gammaretrovirus found in a human prostate cancer cell line called 22Rv1. Using phylogenetic techniques we could show that the sequences in the cell line were more diverse and parental to those derived from patients. We also found that some XMRV sequences were identical to another known gammaretrovirus called Moloney MLV, a virus that is commonly used to study MLV and that cannot replicate in human cells. We concluded that XMRV sequences in patients could be explained by contamination, a recognised problem with very sensitive PCR based detection methods. We went on to show that human integration site junctions described as proving XMRV infection of human prostate samples could also most likely be explained by contamination. We also demonstrated that MLV sequences detected in patient samples by Shyh-Ching Lo and colleagues did not represent evolution of XMRV, rather www.investinme.org Page 26 of 36
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