Study of the inflammatory and immunological actions of retroviruses

• Main Author: Lomparski, Christina
• Language: ENG
• Published: 2009
• Subjects: [SDV:IMM] Life Sciences/Immunology; endogenous retroviruses; Multiple Sclerosis; Autoimmunity; Multiple Sclerosis- associated RetroVirus (MSRV); viral envelope; dendritic cells; Toll-like receptors; Experi- mental Autoimmune Encephalomyelitis (EAE)
• Online Access: http://tel.archives-ouvertes.fr/tel-00448647; http://tel.archives-ouvertes.fr/docs/00/44/86/47/PDF/093110.pdf

Endogenous retroviruses (of the HERV-W family) represent about 8% (1%) of our genome. Their endogenous and exogenous forms (MSRV, Multiple Sclerosis-associated RetroVirus) can alter the regulation of the immune system and be involved in inam- matory and autoimmune pathologies (Multiple Sclerosis). The MSRV envelope protein (ENV) stimulates T lymphocytes by acting as a superantigen. It also interacts with mono- cytes and dendritic cells via membrane receptors, thereby provoking inammatory cytokine production. Our studies are based on the characterisation of the immunological cascade leading from the interaction of the viral envelope with its receptor to the pathological inammatory reaction. The work presented in this thesis combines an in vitro cellular and molecular approach with an in vivo validation using an animal model (mouse). The chosen animal model is Experimental Autoimmune Encephalomyelitis (EAE) in which the complete Freund's adjuvant can be replaced by ENV. Its effects on the murine organism are evaluated on several levels: analysis of behaviour (clinical score) and brain (IRM), cellular and molecular analysis of the immune system. Furthermore, we want to generate a transgenic mouse model expressing different ENVs (MSRV/HERV) under the control of different promoters since MSRV/HERV are found only in great apes. This model, of which the rst steps of elaboration are part of this work, will allow us to study the behaviour of the ENV over-expressing animals as well as their brain and the effects on the immune system.