Analysis of ESCRT machinery participation in the replicative cycle of the Zika Virus in human cells

• Grant number: 18/19469-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2018
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Gustavo Kazuo Silva Yamada
• 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 arbovirus belonging to the Flaviviridae family that is related to other viruses in the family, such as yellow fever virus and the dengue virus (DENV). Initially reported in the scientific literature a virus related to a disease of mild symptoms and self-limitation, recent cases of ZIKV infection were correlated with microcephaly and Guillain-Barré syndrome. This fact in combination with the detection of ZIKV in the amniotic fluid of pregnant women in the brain tissues of microcephalic fetuses led to the attribution of neurotrophic properties to ZIKV. Although much remains to be learned about this virus and its pathophysiology, even less is known about its intracellular dynamics and the molecular mechanisms involved in the entry, assembly and replication of this virus in human cells. Viral assembly is a conserved process among the viruses of the Flaviviridae family and, therefore, presents itself as a promising target for antiviral therapy. In this sense, components of ESCRTs (Endosomal Complexes Required for Transport) have recently been implicated in the assembly of some Flaviviruses. However, the molecular basis of the hijacking of this machinery by Flaviviruses, as well as their specific involvement in the replication of ZIKV are not known. This work aims to identify the importance of Tsg101, an ESCRT-I subunit of virus target cells in their replication processes, by silencing this protein and visualising its effects during infection.