Advanced search
Start date
Betweenand

The role of TAM receptors and their ligandd, Gas6, during Zika Virus infection

Grant number: 18/05752-4
Support type:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): September 01, 2018
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Jean Pierre Schatzmann Peron
Grantee:Lilian Gomes de Oliveira
Supervisor abroad: Carla Vanina Rothlin
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Yale University, United States  
Associated to the scholarship:16/21259-0 - 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, BP.MS

Abstract

Zika virus (ZIKV) emerged as a global health problem and demands effort of the scientific community to understand the underlying mechanisms involved in host-virus interaction. ZIKV is part of the flavivirus genus, wich includs Dengue, West Nile, Yellow Fever and many other viruses. As other pathogens, ZIKV also needs host cell receptors, important for invasion. In this context, it is clear the involvement of the phosphatidylserine receptors named TAM: for Tyro3, Axl and Mer (Family TAM). Flaviviruses are enveloped viruses that contain significant amounts of phosphatidylserine and, thus may indirectly interact with TAM receptors by their endogenous ligands, Gas6 and Protein S. This mechanism is called apoptotic mimicry. It induces viral engagement with host cells surface and further internalization. However, the intracellular pathways triggered, and their correlation with resistance or susceptibility to infection is also largely unknown. Studies conducted by our group have observed a possible link between increased expression of TAM receptors and its ligands and ZIKV replication. We observed that recombinant Gas6 in vivo increases viremia and viral load in spleen. Moreover, we also demonstrated that C57BL/6 mice become susceptible to ZIKV congenital. Indeed, the results evidence the relevance of TAM receptors during ZIKV infection, especially for the development of congenital syndrome. However, to a more profound knowledge of the mechanisms, more experiments are needed. For this purpose, this BEPE project, liked to the master project 2016/21259-0, proposes to perform in vitro and in vivo assays with C57BL/6 WT, Axl-/- and Gas6-/- mice to corroborate the aforementioned findings. This is a cutting-edge laboratory, led by Prof. Carla Rothlin, who has an immense experience on the biology of TAM receptors. This research may greatly contribute to a better understanding on the pathogenesis of ZIKV congenital syndrome, correlating it to viral invasion receptors.