Analysis of antiviral factors and exosomes in trophoblasts and newborn monocytes in Zika virus in vitro infection

• Grant number: 16/16840-6
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2016
• End date: November 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Maria Notomi Sato
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Zika Virus (ZKV) is an emergent flavivirus, transmitted by Aedes mosquitoes, causing a primary infection similar to dengue fever and showing remarkable teratogenic potential, particularly fetal microcephaly. Even though ZKV´s ability to infect different cell types, as epithelial cells, neuronal progenitors and cells from the maternal-fetal interface, indicates that this infection exhibits a systemic feature, the dissemination routes and the antiviral immune response profile involved in this process are still poorly understood. In this context, immune cells, as monocytes, could play a key role in the induction of inflammation and transport of viruses to different anatomical sites. In addition, besides the role played by cells in viral pathogenesis, sub cellular components - as exosomes - are also being recognized as prominent regulators of the immune response. They can carry antiviral factors, but can also host viral elements, playing a dubious role in the infection - a tempting hypothesis in the maternal-fetal interface. Therefore, due to the great relevance of monocytes and trophoblasts in congenital viral infections, our work will investigate the relationship between these cells and ZKV under the light of antiviral factors and exosomes. We will study the importance of entry receptors, antiviral signaling pathways and production of inflammatory and chemotactic factors by monocytes and trophoblasts in the response to ZKV as also the proteomic profile of the exosomes produced by these cells. Our results will provide a better understanding of ZKV infection pathogenesis and may help to identify new therapeutic and diagnostic targets. (AU)

Scientific publications

(4)

(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)

YAMADA YOSHIKAWA, FABIO SEITI; EMIDIO TEIXEIRA, FRANCIANE MOURADIAN; SATO, MARIA NOTOMI; DA SILVA OLIVEIRA, LUANDA MARA. Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News be Packaged?. CELLS, v. 8, n. 6, JUN 2019. (16/16840-6, 16/10522-2)

PIETROBON, ANNA J.; YOSHIKAWA, FABIO S. Y.; OLIVEIRA, LUANA M.; PEREIRA, NATALLI Z.; MATOZO, TAIS; DE ALENCAR, BRUNA C.; DUARTE, ALBERTO J. S.; SATO, MARIA N.. ntiviral Response Induced by Toll-Like Receptor (TLR) 7/TLR8 Activation Inhibits Human Immunodeficiency Virus Type 1 Infection in Cord Blood Macrophage. Journal of Infectious Diseases, v. 225, n. 3, p. 510-519, FEB 1 2022. (16/01269-1, 16/16840-6)

YAMADA YOSHIKAWA, FABIO SEITI; SATO, MARIA NOTOMI. What are the implications of silent replication in fetal and newborn monocytes for Zika therapeutic development?. FUTURE VIROLOGY, v. 14, n. 5, p. 3-pg., 2019-05-01. (16/16840-6, 16/09764-1)

YAMADA YOSHIKAWA, FABIO SEITI; PIETROBON, ANNA JULIA; CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; PEREIRA, NATALLI ZANETE; DA SILVA OLIVEIRA, LUANDA MARA; MACHADO, CLARISSE MARTINS; DA SILVA DUARTE, ALBERTO JOSE; SATO, MARIA NOTOMI. Zika Virus Infects Newborn Monocytes Without Triggering a Substantial Cytokine Response. Journal of Infectious Diseases, v. 220, n. 1, p. 32-40, JUL 1 2019. (16/09764-1, 16/16840-6)