Bradykinin enhances Sindbis virus infection in human brain microvascular endothelial cells

Abstract

Submitted by Nuzia Santos ([email protected]) on 2014-12-04T15:11:49Z No. of bitstreams: 1 Bradykinin enhances Sindbis virus infection in human brain microvascular endothelial cells.pdf: 1158448 bytes, checksum: 5c208b59273623f263acf5a38adfebf2 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2014-12-04T15:16:21Z (GMT) No. of bitstreams: 1 Bradykinin enhances Sindbis virus infection in human brain microvascular endothelial cells.pdf: 1158448 bytes, checksum: 5c208b59273623f263acf5a38adfebf2 (MD5)Made available in DSpace on 2014-12-04T15:16:21Z (GMT). No. of bitstreams: 1 Bradykinin enhances Sindbis virus infection in human brain microvascular endothelial cells.pdf: 1158448 bytes, checksum: 5c208b59273623f263acf5a38adfebf2 (MD5) Previous issue date: 2011Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ. BrasilUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ. BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ. BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ. BrasilUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ. BrasilSindbis 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 infection