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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 type:Regular Research Grants
Duration: March 01, 2018 - February 29, 2020
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Jean Pierre Schatzmann Peron
Grantee:Jean Pierre Schatzmann Peron
Home 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)

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)
JEAN PIERRE SCHATZMANN PERON; HELDER NAKAYA. Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE). Clinics, v. 75, p. -, 2020. Web of Science Citations: 1.
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, SEP 13 2019. Web of Science Citations: 0.
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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