Abstract
Multiple sclerosis-associated retroviral element (MSRV) is a retroviral element, the sequence of which served to define the W family of human endogenous retroviruses. MSRV viral particles display proinflammatory activities both in vitro in human mononuclear cell cultures and in vivo in a humanized SCID mice model. To understand the molecular basis of such properties, we have investigated the inflammatory potential of the surface unit of the MSRV envelope protein (ENV-SU), the fraction that is poised to naturally interact with host cells. We report in this study that MSRV ENV-SU induces, in a specific manner, human monocytes to produce major proinflammatory cytokines through engagement of CD14 and TLR4, which are pattern recognition receptors of primary importance in innate immunity. ENV-SU could also trigger a maturation process in human dendritic cells. Finally, ENV-SU endowed dendritic cells with the capacity to support a Th1-like type of Th cell differentiation. The data are discussed in the context of immune responses and chronic proinflammatory disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antibodies, Monoclonal / pharmacology
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Antibodies, Viral / pharmacology
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Cell Separation
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Cells, Cultured
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Cytokines / biosynthesis
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / virology
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Endogenous Retroviruses / immunology
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Endogenous Retroviruses / physiology*
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Gene Products, env / immunology
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Gene Products, env / physiology*
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Humans
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Immunity, Innate*
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Inflammation Mediators / antagonists & inhibitors
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Inflammation Mediators / physiology
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Leukocytes, Mononuclear / virology
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Lipopolysaccharide Receptors / physiology*
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Membrane Proteins / physiology
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Molecular Sequence Data
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Monocytes / immunology
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Monocytes / metabolism
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Monocytes / virology
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Multiple Sclerosis / immunology
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Multiple Sclerosis / metabolism
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Multiple Sclerosis / virology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th1 Cells / virology*
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Toll-Like Receptor 4 / physiology*
Substances
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Antibodies, Monoclonal
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Antibodies, Viral
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Cytokines
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Gene Products, env
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Inflammation Mediators
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Lipopolysaccharide Receptors
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Membrane Proteins
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TLR4 protein, human
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Toll-Like Receptor 4