title: RIG-I Mediates an Antiviral Response to Crimean-Congo Hemorrhagic Fever Virus.
abstract: In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus (CCHFV), a negative-sense RNA virus with a 5'-monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health implications. We found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV.
  
  
  OBJECTIVE
  CCHFV is a tick-borne virus with a significant public health impact. In order for cells to respond to virus infection, they must recognize the virus as foreign and initiate antiviral signaling. To date, the receptors involved in immune recognition of CCHFV are not known. Here, we investigate and identify RIG-I as a receptor involved in initiating an antiviral response to CCHFV. This receptor initially was not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential viruses recognized by RIG-I.
authors.affiliation: Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Spengler
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Jenish R
authors.initials: JR
authors.lastname: Patel
authors.affiliation: Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ayan K
authors.initials: AK
authors.lastname: Chakrabarti
authors.affiliation: Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Marko
authors.initials: M
authors.lastname: Zivcec
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
authors.affiliation: Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA ebergeron@cdc.gov.
authors.forename: Éric
authors.identifier: http://orcid.org/0000-0003-3398-8628
authors.initials: É
authors.lastname: Bergeron
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D016679:Genome, Viral; D057809:HEK293 Cells; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; C505371:MAVS protein, human; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011971:Receptors, Immunologic; D011991:Receptors, Virus; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases