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TAM receptors and their ligands Gas6 and Pros1 on the ZIKV Congenital Syndrome in Experimental Models

Grant number: 17/22504-1
Support Opportunities:Regular Research Grants
Start date: March 01, 2018
End date: February 29, 2020
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Jean Pierre Schatzmann Peron
Grantee:Jean Pierre Schatzmann Peron
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

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, we will perform in vitro and in vivo. SJL mice will be infected during gestation in the presence or not of Gas6 or RU428, an Axl quinase blocker. We will focus on the role of Axl on the vertical transmission, as well as in the pathogenesis of the central nervous system lesions. The results obtained will not only point to the relevance ofr TAM receptors on the pathogenesis of the disease, but also as its potential as a resistance or susceptibility marker (AU)

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Scientific publications (16)
(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)
BRANDAO, W. N.; DE OLIVEIRA, M. G.; ANDREONI, R. T.; NAKAYA, H.; FARIAS, A. S.; PERON, J. P. S.. Neuroinflammation at single cell level: What is new?. Journal of Leukocyte Biology, . (13/08216-2, 18/21934-5, 17/50137-3, 17/26170-0, 12/19278-6, 17/22504-1, 17/21363-5, 18/14933-2, 19/06372-3)
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, . (16/21259-0, 17/22504-1, 17/26170-0)
BRAGA, TARCIO TEODORO; BRANDAO, WESLEY NOGUEIRA; AZEVEDO, HATYLAS; TERRA, FERNANDA FERNANDES; MELO, AMANDA CAMPELO L.; PEREIRA, FELIPE VALENCA; ANDRADE-OLIVEIRA, VINICIUS; HIYANE, MEIRE IOSHIE; PERON, JEAN PIERRE S.; SARAIVA CAMARA, NIELS OLSEN. NLRP3 gain-of-function in CD4(+) T lymphocytes ameliorates experimental autoimmune encephalomyelitis. Clinical Science, v. 133, n. 17, p. 1901-1916, . (17/05264-7, 17/22504-1, 14/06992-8)
POLONIO, CAROLINA M.; DA SILVA, PATRICK; RUSSO, FABIELE B.; HYPPOLITO, BRENDO R. N.; ZANLUQUI, NAGELA G.; BENAZZATO, CECILIA; BELTRAO-BRAGA, PATRICIA C. B.; MUXEL, SANDRA M.; PERON, JEAN PIERRE S.. microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 18, p. 19-pg., . (20/06145-4, 17/11828-0, 17/26170-0, 21/01717-2, 18/16748-8, 17/22504-1, 22/00291-4, 16/07371-2, 19/13731-0)
DE OLIVEIRA, LILIAN GOMES; ANGELO, YAN DE SOUZA; IGLESIAS, ANTONIO H.; PERON, JEAN PIERRE SCHATZMANN. Unraveling the Link Between Mitochondrial Dynamics and Neuroinflammation. FRONTIERS IN IMMUNOLOGY, v. 12, . (17/22504-1)
BRANDAO, W. N.; DE OLIVEIRA, M. G.; ANDREONI, R. T.; NAKAYA, H.; FARIAS, A. S.; PERON, J. P. S.. Neuroinflammation at single cell level: What is new?. Journal of Leukocyte Biology, v. 108, n. 4, p. 9-pg., . (17/22504-1, 13/08216-2, 18/14933-2, 19/06372-3, 17/21363-5, 17/26170-0, 12/19278-6, 17/50137-3, 18/21934-5)
POLONIO, CAROLINA MANGANELI; DE FREITAS, CARLA LONGO; DE OLIVEIRA, MARILIA GARCIA; ROSSATO, CRISTIANO; BRANDAO, WESLEY NOGUEIRA; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; NISHIYAMA MIMURA, LUIZA AYUMI; BARROS SILVA, MAYSA BRAGA; GARCIA CALICH, VERA LUCIA; et al. Murine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression. Clinical Science, v. 135, n. 9, p. 1065-1082, . (18/10242-5, 17/22504-1, 17/11828-0, 16/07371-2, 17/26170-0)
GIOVANNONI, FEDERICO; BOSCH, IRENE; POLONIO, CAROLINA MANGANELI; TORTI, MARIA F.; WHEELER, MICHAEL A.; LI, ZHAORONG; ROMORINI, LEONARDO; RODRIGUEZ VARELA, MARIA S.; ROTHHAMMER, VEIT; BARROSO, ANDREIA; et al. AHR is a Zika virus host factor and a candidate target for antiviral therapy. NATURE NEUROSCIENCE, v. 23, n. 8, . (17/11828-0, 17/22504-1, 16/07371-2, 17/26170-0)
BANDEIRA, ISABELLE PASTOR; DE ALMEIDA FRANZOI, ANDRE EDUARDO; WOLLMANN, GIULIA MURILLO; GOMES DE MEDEIROS JUNIOR, WASHIGTON LUIZ; BRANDAO, WESLEY NOGUEIRA; SCHATZMANN PERON, JEAN PIERRE; BECKER, JEFFERSON; MOREIRA NASCIMENTO, OSVALDO JOSE; MAGNO GONCALVES, MARCUS VINICIUS. Interleukin-31 and soluble CD40L: new candidate serum biomarkers that predict therapeutic response in multiple sclerosis. NEUROLOGICAL SCIENCES, v. 43, n. 11, p. 8-pg., . (17/22504-1, 17/26170-0)
PERON, J. P. S.; NAKAYA, H., I; SCHLINDWEIN, M. A. M.; GONCALVES, M. V. M.. COVID-19 Pandemic and Dysbiosis: Can the Ivermectin Hysteria Lead to an Increase of Autoimmune Neuroinflammatory Diseases?. CRITICAL REVIEWS IN IMMUNOLOGY, v. 40, n. 6, p. 6-pg., . (17/22504-1, 19/06372-3, 13/08216-2, 17/21363-5, 18/14933-2, 18/21934-5, 12/19278-6)
PERON, J. P. S.; NAKAYA, I, H.; SCHLINDWEIN, M. A. M.; GONCALVES, M. V. M.. COVID-19 Pandemic and Dysbiosis: Can the Ivermectin Hysteria Lead to an Increase of Autoimmune Neuroinflammatory Diseases?. CRITICAL REVIEWS IN IMMUNOLOGY, v. 40, n. 6, SI, p. 537-542, . (17/22504-1, 18/14933-2, 12/19278-6, 13/08216-2, 18/21934-5, 19/06372-3, 17/21363-5)
DE FREITAS, CARLA LONGO; POLONIO, CAROLINA MANGANELI; BRANDAO, WESLEY NOGUEIRA; ROSSATO, CRISTIANO; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; DE OLIVEIRA, MARILIA GARCIA; EVANGELISTA, LUCILA PIRES; HALPERN, SILVIO; MALUF, MARIANGELA; et al. Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System. STEM CELL REVIEWS AND REPORTS, . (20/06145-4, 16/07371-2, 18/10242-5, 17/11828-0, 17/22504-1, 17/26170-0)
BANDEIRA, ISABELLE PASTOR; MACHADO SCHLINDWEIN, MARCO ANTONIO; BREIS, LETICIA CAROLINE; SCHATZMANN PERON, JEAN PIERRE; MAGNO GONCALVES, MARCUS VINICIUS; GUEST, PC. Neurological Complications of the COVID-19 Pandemic: What Have We Got So Far?. CLINICAL, BIOLOGICAL AND MOLECULAR ASPECTS OF COVID-19, v. 1321, p. 11-pg., . (17/22504-1, 17/26170-0)
POLONIO, CAROLINA MANGANELI; PERON, JEAN PIERRE SCHATZMANN. ZIKV Infection and miRNA Network in Pathogenesis and Immune Response. Viruses-Basel, v. 13, n. 10, . (19/13731-0, 17/26170-0, 20/06145-4, 17/11828-0, 17/22504-1)
DE MENDONCA-VIEIRA, LEILA RODRIGUES; ANIBAL-SILVA, CONCEICAO ELIDIANNE; MENEZES-NETO, ARMANDO; NEVES AZEVEDO, ELISA DE ALMEIDA; ZANLUQUI, NAGELA GHABDAN; SCHATZMANN PERON, JEAN PIERRE; DE OLIVEIRA FRANCA, RAFAEL FREITAS. Reactive Oxygen Species (ROS) Are Not a Key Determinant for Zika Virus-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells. Viruses-Basel, v. 13, n. 11, . (16/07371-2, 17/22504-1, 17/26170-0)