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The role of TAM receptors and their ligands, Gas6 and Pros 1 during infection by Zika virus in bone marrow-derived dendritic cells and macrophages of SJL and C57BL/6 mice

Grant number: 16/21259-0
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2017
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Jean Pierre Schatzmann Peron
Grantee:Lilian Gomes de Oliveira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:11/18703-2 - The role of Indoleamine-2,3-dioxigenase and the Triptophan - Kynurenines axis through NMDA receptors over the immune response in the EAE and stroke model, AP.JP
Associated scholarship(s):18/05752-4 - The role of TAM receptors and their ligand, Gas6, during Zika virus infection, BE.EP.MS

Abstract

The Zika virus (ZIKV) emerges as a global health problem and demands efforts of the scientific community to understand the underlying mechanisms involved in the host cell infection. The ZIKV is part of the flavivirus genus, such as Dengue virus, whose cellular invasion mechanism has been elucidated in the literature. It is clear the involvement of Axl receptor Tyro3 and Mer (Family TAM) and its ligands, Gas6 and Protein S, during infection of Dengue virus, a phosphatidylserine-dependent phagocytosis mechanism. Studies conducted by our group showed a possible link between increased expression of TAM receptors and the infection of ZIKV, as well as the susceptibility of SJL mouse strain to ZIKV infection. However, further studies are needed to prove the role of TAM receptors in ZIKV infection and its relationship with susceptibility and resistance of SJL and C57BL/6 strains, respectively. Thus, this study aims to assess the relevance of TAM receptors in ZIKV infection in different individuals through comparisons between mouse strains, and perhaps unravel the basis of the pathogenesis of microcephaly caused by ZIKV in SJL mice. For this purpose, will perform in vitro assays of macrophages and dendritic cells infection derived from SJL mice and C57BL/6 mice, and will use the qPCR analysis, flow cytometry and western blotting techniques to evaluate the expression levels, to measure viral potential to bind and internalize in the target cells and the activation of TAM receptors. (AU)

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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; AMORIM, MARIENE R.; FORATO, JULIA; MURARO, STEFANIE P.; DE SOUZA, GABRIELA F.; MARTINI, MATHEUS C.; BISPO-DOS-SANTOS, KARINA; VIEIRA, ALINE; JUDICE, CARLA C.; PASTORE, GLAUCIA M.; AMARAL, ELIANA; PASSINI JUNIOR, RENATO; MAYER-MILANEZ, HELAINE M. B. P.; RIBEIRO-DO-VALLE, CAROLINA C.; CALIL, ROSELI; BENNINI JUNIOR, JOAO RENATO; LAJOS, GIULIANE J.; ALTEMANI, ALBINA; NOLASCO DA SILVA, MARCOS T.; COAN, ANA CAROLINA; COLELLA-SANTOS, MARIA FRANCISCA; VON ZUBEN, ANDREA P. B.; VINOLO, MARCO AURELIO R.; ARNS, CLARICE WEIS; CATHARINO, RODRIGO RAMOS; COSTA, MARIA LAURA; ANGERAMI, RODRIGO N.; FREITAS, ANDRE R. R.; RESENDE, MARIANGELA R.; GARCIA, MARCIA T.; MORETTI, MARIA LUIZA; RENIA, LAURENT; NG, LISA F. P.; ROTHLIN, V, CARLA; COSTA, FABIO T. M.; SCHATZMANN PERON, JEAN PIERRE; PROENCA-MODENA, JOSE LUIZ. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. BRAIN BEHAVIOR AND IMMUNITY, v. 97, p. 260-274, OCT 2021. Web of Science Citations: 1.
OLIVEIRA, LILIAN G.; SCHATZMANN PERON, JEAN PIERRE. Viral receptors for flaviviruses: Not only gatekeepers. Journal of Leukocyte Biology, v. 106, n. 3, SI, p. 695-701, SEP 2019. Web of Science Citations: 1.

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