title: Toll-like receptor 3 (TLR3) plays a major role in the formation of rabies virus Negri Bodies.
abstract: Human neurons express the innate immune response receptor, Toll-like receptor 3 (TLR3). TLR3 levels are increased in pathological conditions such as brain virus infection. Here, we further investigated the production, cellular localisation, and function of neuronal TLR3 during neuronotropic rabies virus (RABV) infection in human neuronal cells. Following RABV infection, TLR3 is not only present in endosomes, as observed in the absence of infection, but also in detergent-resistant perinuclear inclusion bodies. As well as TLR3, these inclusion bodies contain the viral genome and viral proteins (N and P, but not G). The size and composition of inclusion bodies and the absence of a surrounding membrane, as shown by electron microscopy, suggest they correspond to the previously described Negri Bodies (NBs). NBs are not formed in the absence of TLR3, and TLR3(-/-) mice -- in which brain tissue was less severely infected -- had a better survival rate than WT mice. These observations demonstrate that TLR3 is a major molecule involved in the spatial arrangement of RABV-induced NBs and viral replication. This study shows how viruses can exploit cellular proteins and compartmentalisation for their own benefit.
authors.affiliation: Neuroimmunologie Virale, Institut Pasteur, Paris, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Ménager
authors.forename: Pascal
authors.initials: P
authors.lastname: Roux
authors.forename: Françoise
authors.initials: F
authors.lastname: Mégret
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bourgeois
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Le Sourd
authors.forename: Anne
authors.initials: A
authors.lastname: Danckaert
authors.forename: Mireille
authors.initials: M
authors.lastname: Lafage
authors.forename: Christophe
authors.initials: C
authors.lastname: Préhaud
authors.forename: Monique
authors.initials: M
authors.lastname: Lafon
mesh_terms: D000818:Animals; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D006801:Humans; D007181:Inclusion Bodies, Viral / Q000276:immunology / Q000378:metabolism / Q000821:virology; D053208:Kaplan-Meier Estimate; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D019251:Nucleocapsid / Q000378:metabolism; D011818:Rabies / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D011820:Rabies virus / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3