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The role of mTORC1 e mTORC2 complexes in astrocytes during neurogenesis and physiopathology of Zika virus microcephaly in murine experimental model.

Grant number: 19/15913-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2021
Effective date (End): September 29, 2024
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Jean Pierre Schatzmann Peron
Grantee:Lilian Gomes de Oliveira
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:17/26170-0 - Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination, AP.TEM


Zika virus (ZIKV) has emerged as a global health problem since it was associated with the increase of microcephaly cases in Brazil between 2015 and 2016, however little is known about the mechanisms used by the virus to trigger this condition. ZIKV is part of the Flavivirus genus and has an interesting central nervous system (CNS) tropism, mainly by neuronal progenitor cells (NPCs) and glial cells. Astrocytes are highly abundant glial cells in the CNS and act in an important way for maintenance of neuronal metabolism. This maintenance is mainly due to the production of lactate, via glycolytic pathway, which is an important energetic substrate of neurons. Glycolysis is activated by antiviral cytokines, such as interferon (IFN) type I, and is crucial for maintenance of the antiviral state. In this pathway, the type IFN receptor (IFNAR) leads to the activation of AKT, which activates important complexes that play a role in the translation of interferon-induced genes (ISGs) and in the activation of glycolysis. Such complexes are known as the mechanistic target of rapamycin 1 and 2 (mTORC1 and mTORC2). In this context, it has been reported that ZIKV is able to block both the type I IFN pathway and the activation of AKT-mTOR. In this way, it is plausible to think that ZIKV can antagonize the antiviral immune response and still affect glycolysis leading to neuronal damage and viral replication. The aim of this project is to characterize the role of astrocytes in the pathophysiology of ZIKV microcephaly focusing on the role of mTORC1 and mTORC2 complexes in a murine experimental model. The results obtained may provide data of extreme importance not only about this unknown infection, but also elucidate the CNS lesion mechanisms of infants with microcephaly, which may base, future studies on therapeutic intervention focus

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