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Role of Gas6, ligand of TAM-type receptors, in the pathogenesis of Zika Virus infection in humans

Grant number: 18/13866-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2018
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:João Luiz da Silva Filho
Grantee:Letícia Cristina Scarapicchia Monteiro
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


The Zika Virus (ZIKV) is an arbovirus of the genus Flavivirus, transmitted through the bite of the Aedes aegypti mosquito, which has recently become a public health problem. In the Americas there have been over 200.000 confirmed cases of Zika fever (ZF), with over 60% of those in Brazil alone. Although the infection is generally asymptomatic, recent data show the link between ZIKV infection to neurological sequelae, such as Guillan-Barré syndrome, encephalitis, and meningitis in adults, and to a congenital fetal syndrome that includes fetal microcephaly. Despite the fact that yet all the mechanisms involved in the infection, and how the ZIKV is able to cross barriers formed by endothelial cells (ECs) is unknown, it has been shown that, the TAM family receptors, especially Axl, act as a facilitator for the entry of the virus when it associates with Axl's endogenous ligand (GAS6) (growth arrest-specific 6). Therefore, this project aims to verify the role of Gas6 in the pathogenesis of ZIKV infection, by evaluating the expression of Gas6 and TAM receptors in patients infected by the virus with different degrees of disease severity, and in vitro infection of different human cells. These aims will provide a better understanding of the relationship of the GAS6/TAM receptor axis with the pathogenicity of ZIKV, which may have important therapeutic consequences.

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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)
SILVA-FILHO, JOAO LUIZ; DE OLIVEIRA, LILIAN G.; MONTEIRO, LETICIA; PARISE, PIERINA L.; ZANLUQUI, NAGELA G.; POLONIO, CAROLINA M.; DE FREITAS, CARLA L.; TOLEDO-TEIXEIRA, DANIEL A.; DE SOUZA, WILLIAM M.; BITTENCOURT, NAJARA; et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. BRAIN BEHAVIOR AND IMMUNITY, v. 97, p. 260-274, . (17/26908-0, 16/00194-8, 20/02159-0, 16/21259-0, 18/13866-0, 16/12855-9, 17/22062-9, 17/26170-0, 17/11828-0, 17/02402-0, 20/02448-2, 18/13645-3, 16/07371-2)

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