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.

journal_name

Virology

journal_title

Virology

authors

Rust NM,Papa MP,Scovino AM,da Silva MM,Calzavara-Silva CE,Marques ET Jr,Peçanha LM,Scharfstein J,Arruda LB

doi

10.1016/j.virol.2011.10.003

subject

Has Abstract

pub_date

2012-01-05 00:00:00

pages

81-91

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(11)00471-5

journal_volume

422

pub_type

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