Metabolic alterations induced by Zika virus in prostate cells: metabolomics and oncolytic potential

Author(s)

Jeany Delafiori

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2022-11-25

Examining board members

Rodrigo Ramos Catharino; William Marciel de Souza; Daisy Machado; Catarina Raposo Dias Carneiro; Daniel Fábio Kawano

• Advisor: Rodrigo Ramos Catharino

Abstract

The Zika virus (ZIKV) is a flavivirus of the Flaviviridae family. From 2015 to 2016, the infection was introduced into the Americas and Pacific islands, and the epidemic was associated with neurological complications such as Guillain-Barré syndrome and Congenital Zika syndrome. Given ZIKV clinical and epidemiological importance, studies are necessary to clarify the mechanisms of cellular infection. In highly proliferative cells, such as neural progenitor cells, glioblastoma, and neuroblastoma, ZIKV promotes an antiproliferative effect, suggesting the potential oncolytic effect of this arbovirus in tumor intervention. Additionally, ZIKV has tropism for male reproductive system cells, especially prostate cells that are permissive to persistent infection, suggesting the prostate as a viral replication reservoir and potential implication in male infertility during infection. Persistent ZIKV replication in prostate epithelial cells results in significant changes in cell transcriptome. However, further research is needed to determine the influence of persistent ZIKV infection on the cellular metabolome. Given the multifactor pathogenic characteristic of ZIKV infection, this study used an untargeted metabolomic approach to investigate the metabolic changes induced by ZIKV in prostate cells, seeking the identification of markers of persistent infection and elucidation of its potential oncolytic effect. It was observed that ZIKV affects the viability and metabolism of normal (PNT1a) and tumor (PC-3) prostate cells differently, with PC-3 cells being more susceptible to growth inhibition. In metabolic terms, there are changes in lipid markers that explain the antiproliferative effect of ZIKV in PC-3 cells. Persistent infection in PNT1a cells is mediated by altered levels of glycerolipids, acylcarnitines, fatty acids, oxylipins, and small metabolites resulting from oxidative stress that act as tumor progression mediators. Lipid biosynthesis and metabolism are important aspects of viral infection, and perturbation of this metabolism is shown to be fundamental in the infection outcome of the analyzed cell types, demonstrating the duality in the use of ZIKV as an antitumoral agent (AU)

• FAPESP's process: 19/05718-3 - Determination of metabolic alterations and therapeutic potential of Zika Virus in cancer cells by mass spectrometry and artificial intelligence
• Grantee: Jeany Delafiori
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)