title: Hantaviruses induce antiviral and pro-inflammatory innate immune responses in astrocytic cells and the brain.
abstract: Although hantaviruses are not generally considered neurotropic, neurological complications have been reported occasionally in patients with hemorrhagic fever renal syndrome (HFRS). In this study, we analyzed innate immune responses to hantavirus infection in vitro in human astrocytic cells (A172) and in vivo in suckling ICR mice. Infection of A172 cells with pathogenic Hantaan virus (HTNV) or a novel shrew-borne hantavirus, known as Imjin virus (MJNV), induced activation of antiviral genes and pro-inflammatory cytokines/chemokines. MicroRNA expression profiles of HTNV- and MJNV-infected A172 cells showed distinct changes in a set of miRNAs. Following intraperitoneal inoculation with HTNV or MJNV, suckling ICR mice developed rapidly progressive, fatal central nervous system-associated disease. Immunohistochemical staining of virus-infected mouse brains confirmed the detection of viral antigens within astrocytes. Taken together, these findings suggest that the neurological findings in HFRS patients may be associated with hantavirus-directed modulation of innate immune responses in the brain.
authors.affiliation: 1 Department of Biomedical Sciences, College of Medicine, Korea University , Gurodong, Gurogu, Seoul, Republic of Korea.
authors.forename: Ok Sarah
authors.initials: OS
authors.lastname: Shin
authors.forename: Gabriella Shinyoung
authors.initials: GS
authors.lastname: Song
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.forename: Richard
authors.initials: R
authors.lastname: Yanagihara
authors.forename: Ho-Wang
authors.initials: HW
authors.lastname: Lee
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Song
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D001253:Astrocytes / Q000276:immunology* / Q000821:virology*; D001921:Brain / Q000821:virology; D045744:Cell Line, Tumor; D020805:Central Nervous System Viral Diseases / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006476:Orthohantavirus / Q000276:immunology / Q000502:physiology*; D018778:Hantavirus Infections / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000821:virology; D014779:Virus Replication