The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses.
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.
Rolland
Alexandre
A
Laboratoire d'Immunochimie, Institut National de la Santé et de la Recherche Médicale Unité 548, Commissariat à l'Energie Atomique, Grenoble, France.
Jouvin-Marche
Evelyne
E
Viret
Christophe
C
Faure
Mathias
M
Perron
Hervé
H
Marche
Patrice N
PN
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000914:Antibodies, Viral / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D020077:Endogenous Retroviruses / Q000276:immunology / Q000502:physiology*; D015686:Gene Products, env / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D016207:Cytokines; D015686:Gene Products, env; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4