Basic mechanisms of Friend virus-induced immunomodulation and tumorigenesis (154.34)

Abstract

Abstract Friend murine leukemia Virus (FV) infection of immunocompetent mice is a well established model to acquire further knowledge about retrovirus-associated mechanisms, enabling the development of preventive and therapeutic treatments against retrovirus-induced diseases. Our own studies show that formation of the immunological synapse between FV-infected DCs and T cells is altered. Those DCs induced a regulatory phenotype and suppressive function in cocultured CD4+ T cells (Treg). In order to identify key molecules that contribute to this Treg induction, expression patterns of cytoplasmatic proteins in uninfected and FV-infected DCs were comparatively analyzed by Protein-mass fingerprinting. By that approach about 600 differentially expressed proteins were identified. Interestingly, many of these are cytoskeletal proteins, and some are known to be involved in DC-T cell interactions (e.g. Myosins1F, 9, and 14). Notably, several MHCII antigens are downregulated in FV-infected DCs as compared with uninfected DCs. Recent studies show that the endocytic capacity of FV-infected DCs was significantly enhanced as compared with control DCs. Our current work is focussed on elucidating the function of signalling proteins which are differentially expressed in FV-infected vs. uninfected DCs. Taken together, our work is aimed to understand how retroviral infection of DCs alters DC-T cell interactions, and at which extent these effects contribute to retrovirus-induced immunosuppression.