title: Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity.
abstract: Viral nucleic acids often trigger an innate immune response in infected cells. Many viruses, including hepatitis C virus (HCV), have evolved mechanisms to evade intracellular recognition. Nevertheless, HCV-permissive cells can trigger a viral RNA-, TLR7-, and cell-contact-dependent compensatory interferon response in nonpermissive plasmacytoid dendritic cells (pDCs). Here we report that these events are mediated by transfer of HCV-RNA-containing exosomes from infected cells to pDCs. The exosomal viral RNA transfer is dependent on the endosomal sorting complex required for transport (ESCRT) machinery and on Annexin A2, an RNA-binding protein involved in membrane vesicle trafficking, and is suppressed by exosome release inhibitors. Further, purified concentrated HCV-RNA-containing exosomes are sufficient to activate pDCs. Thus, vesicular sequestration and exosomal export of viral RNA may serve both as a viral strategy to evade pathogen sensing within infected cells and as a host strategy to induce an unopposed innate response in replication-nonpermissive bystander cells.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. marlene.dreux@ens-lyon.fr
authors.forename: Marlène
authors.initials: M
authors.lastname: Dreux
authors.forename: Urtzi
authors.initials: U
authors.lastname: Garaigorta
authors.forename: Bryan
authors.initials: B
authors.lastname: Boyd
authors.forename: Elodie
authors.initials: E
authors.lastname: Décembre
authors.forename: Josan
authors.initials: J
authors.lastname: Chung
authors.forename: Christina
authors.initials: C
authors.lastname: Whitten-Bauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieland
authors.forename: Francis V
authors.initials: FV
authors.lastname: Chisari
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D055354:Exosomes / Q000378:metabolism* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D012367:RNA, Viral / Q000276:immunology* / Q000378:metabolism*
chemical_list: D012367:RNA, Viral