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Zika virus and the placental barrier: the role of immune markers and cellular receptors on viral infection and activation of endothelial cells

Grant number: 17/12957-9
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2017
Effective date (End): August 31, 2021
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Fabio Trindade Maranhão Costa
Grantee:Louis Thomson Hey
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:16/00194-8 - Pathogenesis and neurovirulence of emerging viruses in Brazil, AP.JP

Abstract

Zika Virus (ZIKV) represents a public health challenge to Brazil and the rest of the world. Since its introduction to the continent in 2014, there have been over 200.000 confirmed cases of Zika Fever (ZF) in the Americas; with over 60% of those in Brazil alone. ZIKV infection has been linked to neurological sequelae, such as Guillan-Barré Syndrome, Encephalitis, and Meningitis. It has also been linked to a Congenital Fetal Syndrome that includes fetal microcephaly. Yet the mechanism by which the virus crosses the placental and fetal Blood-Brain Barrier (BBB) remains unknown. These barriers are lined by endothelial cells, which normally prevent viral infections from crossing. Cytokines play a role in endothelial barrier modulation, and have been important in understanding the closely related Dengue Virus fever. Recently, our group has published the first major study of cytokine dynamics in human ZF patients. This study aims to further explore the role of cytokines on endothelial activation and barrier function during ZIKV infection. Additionally, it aims characterize the membrane receptor(s) responsible for ZIKV entry into endothelial cells. These aims will provide clinicians with resources to better predict ZF outcomes, and may provide insights leading to a ZIKV vaccine or therapy. (AU)