Institut de Génétique Moléculaire de Montpellier (IGMM) - UMR5535


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Home page > Research Groups > Marc SITBON - Retroviruses, Envelopes and Metabolic Markers

Marc SITBON - Retroviruses, Envelopes and Metabolic Markers

Retroviruses provide information on virus-cell interactions and pathogenesis, as well as on eukaryotic gene expression. Moreover, the distinctive ability of retrovirus envelope glycoproteins to bind specific receptors can be used to design new cell differentiation markers and tools for cell- specific gene transfer strategies. Using a wide array of techniques, we study cell type-dependent retroviral replication, infection, pathogenesis and gene transfer in several human and animal models, including mouse, simian and human retroviruses.

We are interested in all aspects of infection by retroviruses and their co-evolution with their mammalian hosts. We study the molecular bases of virus-host interactions, their impact on cellular metabolism, retrovirus pathophysiology and epidemiology, and explore the use of retroviruses in gene transfer. Our main models make use of human and simian retroviruses (the HTLV and STLV T cell leukemia viruses and the HIV and SIV immunodeficiency viruses), and mouse pathogenesis models with murine leukemia viruses (MLV). In vivo infection and spreading of retroviruses are based on cell-to-cell contacts that are likely to create higher local multiplicity of infection, or MOI, than in cell-free infection models that are generally used ex vivo. In this context, innate mechanisms of resistance to the early steps of retroviral replication are of major importance. We use mouse, human and simian ex vivo and in vivo models of retrovirus infections to study early steps of retroviral replication and both oncogenic and non-oncogenic potential pathogenic effects. One of the earliest events that conditions a successful infection is the interaction of the virus-encoded envelope glycoprotein (Env) with cell surface components that act as receptors for viral entry. We have shown that the env genes of the otherwise distant MLV and HTLV present close phylogenetic and functional relatedness. This and other observations led us to postulate that mammalian retroviruses evolved by independent “env captures”, selected on a role played by ancestral Env in virion formation and egress, in addition to viral entry. We derived new Env-derived tools that allowed us to identify the HTLV Env receptor as Glut1, the main vertebrate glucose transporter. We distinguished Glut1 extracellular loops responsible for binding and post-binding events and showed that Glut1 transporter activity is inhibited upon interaction with the HTLV Env receptor-binding domain. We isolated and tagged HTLV and other retrovirus Env-derived receptor-binding domains to monitor the physiological surface expression of Glut1 and other nutrient transporters in natural contexts. We are also extending this approach to different retroviruses whose receptors remain unknown. We will continue using different retrovirus models to better understand in vivo.

Institut de Génétique Moléculaire de Montpellier
CNRS-UMR 5535 - 1919, Route de Mende - 34293 Montpellier  Cedex 5
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