The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses.

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.

• Authors: Alexandre Rolland, Evelyne Jouvin-Marche, Christophe Viret, Mathias Faure, Hervé Perron, Patrice N Marche
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 12 Pg. 7636-44 (Jun 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16751411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Viral
• Cytokines
• Gene Products, env
• Inflammation Mediators
• Lipopolysaccharide Receptors
• Membrane Proteins
• TLR4 protein, human
• Toll-Like Receptor 4

Topics

• Amino Acid Sequence
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Viral (pharmacology)
• Cell Separation
• Cells, Cultured
• Cytokines (biosynthesis)
• Dendritic Cells (immunology, metabolism, virology)
• Endogenous Retroviruses (immunology, physiology)
• Gene Products, env (immunology, physiology)
• Humans
• Immunity, Innate
• Inflammation Mediators (antagonists & inhibitors, physiology)
• Leukocytes, Mononuclear (immunology, metabolism, virology)
• Lipopolysaccharide Receptors (physiology)
• Membrane Proteins (physiology)
• Molecular Sequence Data
• Monocytes (immunology, metabolism, virology)
• Multiple Sclerosis (immunology, metabolism, virology)
• Th1 Cells (immunology, metabolism, virology)
• Toll-Like Receptor 4 (physiology)