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Mechanisms involved in the assembly and externalization of Zika virus in human cells.

Grant number: 16/05945-1
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): June 01, 2016
Effective date (End): May 31, 2018
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Luis Lamberti Pinto da Silva
Grantee:Roberta Maraninchi Silveira
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/02438-6 - Studies with Bunyaviridae that produce human disease, AP.TEM

Abstract

The Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, genus Flavivirus that is transmitted by Aedes mosquitoes. Despite its emerging importance in public health very little is known about the molecular mechanisms controlling its replication cycle in human cells. Therefore, this project aims to investigate the mechanisms involved in the assembly and externalization of ZIKV and the participation of the cell's autophagy machinery these processes. Specifically, we will identify the compartments of the cell that serve as platforms for viral assembly and search for host cell factors potentially required. We will also study the role played by the cell autophagy machinery in viral replication and how the ZIKV interferes with the autophagic flux. Although, the autophagic degradation activity may represent one of the strategies used by cells in the defense against viral infection, recent evidence indicates that ZIKV hijacks this machinery to promote its replication. Autophagy plays an important role in the energetic balance and tissue homeostasis, particularly in nervous tissues. Moreover, autophagy is essential for the correct development and functioning of the central nervous system. A likely relationship between vertical transmission of ZIKV and fetal microcephaly has raised questions about the molecular mechanisms implicated in the abnormal development of the brain caused by ZIKV, and a better understanding of how the virus interferes with autophagy may contribute to answer these questions. Finally, a better compression of ZIKV replication cycle may contribute to the development of strategies aimed at inhibiting viral replication.

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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)
TAVARES, LUCAS A.; DE CARVALHO, V, JULIANNE; COSTA, CRISTINA S.; SILVEIRA, ROBERTA M.; DE CARVALHO, ANDREIA N.; DONADI, EDUARDO A.; DASILVA, LUIS L. P.. Two Functional Variants of AP-1 Complexes Composed of either gamma 2 or gamma 1 Subunits Are Independently Required for Major Histocompatibility Complex Class I Downregulation by HIV-1 Nef. Journal of Virology, v. 94, n. 7, . (16/05945-1, 16/18207-9, 15/26667-7, 14/02438-6, 18/08966-5, 18/00297-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVEIRA, Roberta Maraninchi. Subcellular localization of Zika virus during infection in human cells. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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