title: Essential role of RIG-I in the activation of endothelial cells by dengue virus.
abstract: Dengue virus (DENV) infection is associated to exacerbated inflammatory response and structural and functional alterations in the vascular endothelium. However, the mechanisms underlying DENV-induced endothelial cell activation and their role in the inflammatory response were not investigated so far. We demonstrated that human brain microvascular endothelial cells (HBMECs) are susceptible to DENV infection, which induces the expression of the cytoplasmic pattern recognition receptor (PRR) RIG-I. Infection of HBMECs promoted an increase in the production of type I IFN and proinflammatory cytokines, which were abolished after RIG-I silencing. DENV-infected HBMECs also presented a higher ICAM-1 expression dependent on RIG-I activation as well. On the other hand, ablation of RIG-I did not interfere with virus replication. Our data suggest that RIG-I activation by DENV may participate in the disease pathogenesis through the modulation of cytokine release and expression of adhesion molecules, probably contributing to leukocyte recruitment and amplification of the inflammatory response.
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, CCS, Bloco E, lab. E-018. Av. Carlos Chagas Filho, 373. Cidade Universitária, Rio de Janeiro, RJ, Brazil.
authors.forename: Thaís Moraes
authors.initials: TM
authors.lastname: da Conceição
authors.forename: Naiara Miranda
authors.initials: NM
authors.lastname: Rust
authors.forename: Ana Carolina Egypto Rosa
authors.initials: AC
authors.lastname: Berbel
authors.forename: Nathalia Balthazar
authors.initials: NB
authors.lastname: Martins
authors.forename: Carlos Antonio
authors.initials: CA
authors.lastname: do Nascimento Santos
authors.forename: Andrea Thompson
authors.initials: AT
authors.lastname: Da Poian
authors.forename: Luciana Barros
authors.initials: LB
authors.lastname: de Arruda
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D003715:Dengue / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000276:immunology* / Q000821:virology*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta / Q000096:biosynthesis; D008833:Microcirculation; D011971:Receptors, Immunologic; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C573420:ICAM1 protein, human; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases