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Role of inflammasomes in the control of ZIKV infection in glial cells

Grant number: 18/19411-4
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Karina Ramalho Bortoluci
Grantee:Ingrid Sancho de Farias
Home Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The Zika virus (ZIKV) is an Arbovirus belonging to the family Flaviviridae of the genus Flavivirus, described for the first time in 1974 in Uguanda. In 2007, the transmission by the Aedes aegypti mosquito caused the first epidemic in Micronesia, leading to a worldwide warning about the severity of the symptoms by infected individuals. In 2013, the ZIKV spread through Brazil and others Latin American countries. A first association of ZIKV and neurological disorders occurred in 2013-2014, when was an increase in the number of cases of Guillain-Barré syndrome and microcephaly. Until now, little is know about the innate immune response against this virus and the elucidation of the mechanisms involving its control has become of extreme importance. One of the components of the innate immunity are the inflammasomes, which are multiprotein platforms present in the cellular cytosol capable of activating caspase-1 protease culminating on the cleavage of proinflammatory cytokines IL-1b and IL-18. When activated, caspase-1 can cleave the pore-forming protein Gasdermin D (GSDMD), resulting in an inflammatory cell death called piroptosis. Studies have shown that ZIKV has a tropism by Central Nervous System (CNS) cells, being able to infect glial cells (like microglia and astrocytes) and trigger an immune response, whose consequences need to be elucidated. Since effector responses mediated by inflammasomes can contribute to both viral control and exacerbation of infection-related pathology, the central objective of the present project is to investigate the consequences of the activation of inflammasomes by ZIKV in glial cells. (AU)