title: Interactions of human microglia cells with Japanese encephalitis virus.
abstract: Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans. Severe Japanese encephalitis cases display strong inflammatory responses in the central nervous system and an accumulation of viral particles in specific brain regions. Microglia cells are the unique brain-resident immune cell population with potent migratory functions and have been proposed to act as a viral reservoir for JEV. Animal models suggest that the targeting of microglia by JEV is partially responsible for inflammatory reactions in the brain. Nevertheless, the interactions between human microglia and JEV are poorly documented.
  
  
  
  Using human primary microglia and a new model of human blood monocyte-derived microglia, the present study explores the interaction between human microglia and JEV as well as the role of these cells in viral transmission to susceptible cells. To achieve this work, vaccine-containing inactivated JEV and two live JEV strains were applied on human microglia.
  
  
  
  Live JEV was non-cytopathogenic to human microglia but increased levels of CCL2, CXCL9 and CXCL10 in such cultures. Furthermore, human microglia up-regulated the expression of the fraktalkine receptor CX3CR1 upon exposure to both JEV vaccine and live JEV. Although JEV vaccine enhanced MHC class II on all microglia, live JEV enhanced MHC class II mainly on CX3CR1+microglia cells. Importantly, human microglia supported JEV replication, but infectivity was only transmitted to neighbouring cells in a contact-dependent manner.
  
  
  
  Our findings suggest that human microglia may be a source of neuronal infection and sustain JEV brain pathogenesis.
authors.affiliation: Department of Medicine, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland. nils.lannes@unifr.ch.
authors.forename: Nils
authors.initials: N
authors.lastname: Lannes
authors.affiliation: Department of Medicine, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland.
authors.forename: Viviane
authors.initials: V
authors.lastname: Neuhaus
authors.affiliation: Department of Medicine, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Scolari
authors.affiliation: Department of Medicine, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland.
authors.forename: Solange
authors.initials: S
authors.lastname: Kharoubi-Hess
authors.affiliation: Department of Medicine, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Walch
authors.affiliation: Institute of Virology and Immunology, Sensemattstrasse 293, Mittelhäusern, Switzerland.|Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Langassstrasse 122, Bern, Switzerland.
authors.forename: Artur
authors.initials: A
authors.lastname: Summerfield
authors.affiliation: Department of Medicine, Unit of Anatomy, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland.
authors.forename: Luis
authors.initials: L
authors.lastname: Filgueira
mesh_terms: D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D004664:Encephalitis Virus, Japanese / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D017628:Microglia / Q000821:virology*; D014779:Virus Replication
chemical_list: D018925:Chemokines
keywords: Chemokine ligand-receptor; Human microglia; Inflammation; Japanese encephalitis virus; Viral transmission