title: Bradykinin enhances Sindbis virus infection in human brain microvascular endothelial cells.
abstract: Sindbis virus (SINV) induces inflammatory and vasoactive responses that are associated with rash and arthritis in human infections. The mechanisms underlying infection-associated microvasculopathy are still unknown. We investigated whether endothelial cells infected by SINV are differentially responsive to bradykinin (BK), a potent inducer of inflammatory edema in a broad range of infectious diseases. Human endothelial cells (HBMECs) infected with SINV presented an upregulation of bradykinin B2 receptors (BK2R) expression. Also, BK reduced SINV-induced apoptosis and enhanced virus replication in HBMECs in a way dependent on BK2R, PI3 kinase and ERK signaling. Strikingly, intracerebral infection of mice in the presence of a BK2R antagonist reduced the local viral load. Our data suggest that SINV infection renders human endothelial cells hypersensitive to BK, which increases host cell survival and viral replication. Ongoing studies may clarify if the deregulation of the kinin pathway contributes to infection-associated vasculopathies in life-threatening arbovirus infections.
authors: Departamento de Virologia, Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil.
authors: Naiara Miranda
authors: NM
authors: Rust
authors: Michelle Premazzi
authors: MP
authors: Papa
authors: Aline Miranda
authors: AM
authors: Scovino
authors: Mayara Marques Carneiro
authors: MM
authors: da Silva
authors: Carlos Eduardo
authors: CE
authors: Calzavara-Silva
authors: Ernesto Torres de Azevedo
authors: ET
authors: Marques
authors: Ligia Maria Torres
authors: LM
authors: Peçanha
authors: Julio
authors: J
authors: Scharfstein
authors: Luciana B
authors: LB
authors: Arruda
mesh_terms: D018354:Alphavirus Infections / Q000378:metabolism / Q000821:virology*; D000818:Animals; D017209:Apoptosis; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D001921:Brain / Q000098:blood supply / Q000821:virology; D002460:Cell Line; D002470:Cell Survival; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012845:Sindbis Virus / Q000502:physiology*; D014709:Vero Cells; D019562:Viral Load / Q000187:drug effects; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D001920:Bradykinin; D065094:Bradykinin B2 Receptor Antagonists; D019869:Phosphatidylinositol 3-Kinases; D043782:Receptor, Bradykinin B2; D014764:Viral Proteins