1 Department of Biomedicine - Medical Microbiology and Immunology, Department of Biomedicine, Health, Aarhus University2 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University3 Department of Clinical Medicine - The Department of Neurology, Department of Clinical Medicine, Health, Aarhus University4 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University5 Department of Clinical Medicine - The Department of Neurology, Department of Clinical Medicine, Health, Aarhus University
Background: Multiple sclerosis (MS) is a demyelinating, inflammatory disease of the central nervous system (CNS). MS is mediated by the immune system but the etiology of the disease remains unknown. Retroviral envelope (Env) proteins, encoded by human endogenous retroviruses (HERVs), are expressed in increased amounts on B cells from MS patients. Furthermore, the amount of anti-HERV antibodies in serum and cerebrospinal fluid from patients with MS is increased when compared with healthy controls. Aim: The overall aim of this project is to investigate the potential role of HERVs in the development of MS and the possible direct pathogenic effects of HERV-encoded Env proteins on the CNS. Methods: Construction and characterization of a panel of recombinant Env-proteins is initiated and their pathogenic potential will be investigated: Fusiogenic potential analyzed by flow cytometry and confocal microscopy. Analysis of Env-induced apoptosis/necrosis in CNS cells will be performed by both DNA fragmentation ELISA and qPCR. Furthermore, the cellular localization of HERV-antigens on cells from patients with MS will be determined by confocal microscopy. A flow cytometric/confocal method has been optimized for the detection of expression of HERV-antigens on cells. Results: Preliminary results will be available in 2014. Perspectives: Results will contribute new knowledge of MS pathogenesis and the possible involvement of HERVs herein. A more comprehensive understanding of HERVs in general will also be obtained.
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Aarhus University Graduate School of Health, PhD Day 2014