Establishment of an in vitro model of vascular permeability evaluation to study the hemorrhagic dengue fever pathogenesis and screening of compounds with therapeutic potential

• Grant number: 13/01690-0
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2014 - August 31, 2016
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Ester Cerdeira Sabino
• Grantee: Ester Cerdeira Sabino
• Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Camila Malta Romano ; Francielle Tramontini Gomes de Sousa

Abstract

The bleeding is one of the main signs of complication of dengue virus (DENV) infection, causing dengue hemorrhagic fever (DHF), a severe form of the disease with lethal potential especially in children. The DHF pathogenesis is complicated and multifactorial, involving both viral and host factors. Moreover, the lack of animal models representing satisfactorily the pathophysiology of dengue fever in humans has been limiting the advances in understanding the DHF mechanisms as well as the development of drugs for the DHF treatment. Monocytes are cells responsible for immune response to infection with DENV, producing mediators that interact with endothelia and increasing the vascular leakage in humans. Therefore, the aim of this project is to implement a model for assessing the in vitro vascular permeability using endothelial cells co-cultured with monocytes and infected by DENV in order to study the factors involved in vascular extravasation and to screen compounds that possibly inhibit this process. The endothelial cells will be cultivated on inserts with microporous membranes arranged in culture plates, generating two compartments, apical and basolateral. In this system, the cells infected with DENV can produce cytokines and mediators which will interfere with the in vitro vascular permeability, similarly to the in vivo mechanism. The vascular permeability will be calculated through the addition of fluorescent dextran at the apical site and measurement of its transport to the basolateral compartment. The proposed system will allow us to perform the screening of compounds with therapeutic potential against dengue and to study the interference of different clinical isolates of DENV on vascular permeability and the cytokine production profile in order to better understand the factors that interfere in the pathogenesis of DHF. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, LENNON RAMOS; VICENTIN, ELAINE CRISTINA MATOS; PEREIRA, SARA ARAUJO; MAEDA, DENICAR LINA NASCIMENTO FABRIS; ALVES, RUBENS PRINCE DOS SANTOS; ANDREATA-SANTOS, ROBERT; SOUSA, FRANCIELLE TRAMONTINI GOMES DE; YAMAMOTO, MARCIO MASSAO; CASTRO-AMARANTE, MARIA FERNANDA; FAVARO, MARIANNA TEIXEIRA DE PINHO; et al. Intradermal Delivery of Dendritic Cell-Targeting Chimeric mAbs Genetically Fused to Type 2 Dengue Virus Nonstructural Protein 1. VACCINES, v. 8, n. 4, DEC 2020. (13/26942-2, 14/04303-0, 16/05570-8, 13/01702-9, 13/11442-4, 14/17595-0, 13/01690-0)

FRANCIELLE T. G. SOUSA; CRISTINA NUNES; CAMILA MALTA ROMANO; ESTER CERDEIRA SABINO; MIGUEL ANGEL GONZÁLEZ-CARDENETE. Anti-Zika virus activity of several abietane-type ferruginol analogues. Revista do Instituto de Medicina Tropical de São Paulo, v. 62, 2020-12-07. (13/01690-0, 13/01702-9, 19/03859-9)

GOMES DE SOUSA CARDOZO, FRANCIELLE TRAMONTINI; BAIMUKANOVA, GYULNAR; LANTERI, MARION CHRISTINE; KEATING, SHEILA MARIE; FERREIRA, FREDERICO MORAES; HEITMAN, JOHN; PANNUTI, CLAUDIO SERGIO; PATI, SHIBANI; ROMANO, CAMILA MALTA; SABINO, ESTER CERDEIRA. Serum from dengue virus-infected patients with and without plasma leakage differentially affects endothelial cells barrier function in vitro. PLoS One, v. 12, n. 6, JUN 6 2017. (13/01702-9, 13/01690-0, 12/15381-7)