The role of cell death pathways during the ZIKA virus infection

• Grant number: 17/03603-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2017
• End date: April 04, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ricardo Weinlich
• Grantee: Rafaela da Rosa Ribeiro
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated scholarship(s): 19/09795-2 - CRISPR/Cas9 tool to knockout cell death pathway genes in neuronal cells and its impact under Zika virus infection, BE.EP.PD

Abstract

For a long time, apoptosis was the only type of cell death that occurs during homeostasis andmost of the pathophysiology. It is characterized by organized cell disassembly, which prevents aninflammatory response. On the other hand, necrosis, a passive process that causes extravasation ofthe intracellular content and inflammation, occurs in extreme conditions. Recently, it has beendescribed cell death modes with necrotic phenotype but regulated by biochemical mechanisms.Among them, necroptosis is characterized by a cascade of kinases activation, culminating in theactivation of MLKL (mixed lineage kinase-like), which migrates to the plasma membrane,destabilizing it. Since its discovery, necroptosis has been described as relevant in severalpathologies, such as cancer, autoimmunity and virus infection. In this context, it has recently beenshown that infection by ZIKA virus (ZIKAV), an agent of microcephaly in neonates and otherneurological disorders, has strong potential for tissue destruction. These studies show increasedexpression of apoptosis-related proteins and activation of caspase-3 during infection of cells ofnerve tissue. Although interesting, these data do not exhaust the questions of how ZIKAV promotescell death and whether this is relevant for the observed phenotype. Therefore, this project will use invivo and in vitro models to investigate, in depth, the types of cell death induced by ZIKAV in thedifferent infected cells and whether the blockade of these cell death pathways alter the parametersresulting from the infection.