Influence of Zika virus on the cytotoxicity, cell adhesion, apoptosis and inflammatory markers of glioblastoma cells

Daniel Rodrigo Marinowic; Gabriele Goulart Zanirati; Pamella Nunes Azevedo; Ângela Zanatta; Ismael Plentz; Allan Marinho Alcará; Fernanda Bueno Morrone; Thamiris Becker Scheffel; Angélica Regina Cappellari; Paulo Michel Roehe; Ana Paula Muterle Varela; Denise Cantarelli Machado; Fabiana Spillari Viola; Jaderson Costa Da Costa

doi:10.3892/ol.2024.14309

Influence of Zika virus on the cytotoxicity, cell adhesion, apoptosis and inflammatory markers of glioblastoma cells

Oncol Lett. 2024 Feb 28;27(4):176. doi: 10.3892/ol.2024.14309. eCollection 2024 Apr.

Authors

Daniel Rodrigo Marinowic^{1

2}, Gabriele Goulart Zanirati^{1

3}, Pamella Nunes Azevedo^{1

2}, Ângela Zanatta^{1

2}, Ismael Plentz³, Allan Marinho Alcará^{1

3}, Fernanda Bueno Morrone^{2

4

5}, Thamiris Becker Scheffel^{4

5}, Angélica Regina Cappellari^{4

5}, Paulo Michel Roehe⁶, Ana Paula Muterle Varela⁶, Denise Cantarelli Machado^{1

2}, Fabiana Spillari Viola^{1

2}, Jaderson Costa Da Costa^{1

2

3}

Affiliations

¹ Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil.
² Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
³ Graduate Program in Medicine, Pediatrics and Child Health, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
⁴ Applied Pharmacology Laboratory, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
⁵ Graduate Program in Molecular and Cellular Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
⁶ Laboratory of Virology, Department of Microbiology, Immunology and Parasitology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90040-060, Brazil.

Abstract

Glioblastoma (GBM) is one of the most common types of brain tumor in adults. Despite the availability of treatments for this disease, GBM remains one of the most lethal and difficult types of tumors to treat, and thus, a majority of patients die within 2 years of diagnosis. Infection with Zika virus (ZIKV) inhibits cell proliferation and induces apoptosis, particularly in developing neuronal cells, and thus could potentially be considered an alternative for GBM treatment. In the present study, two GBM cell lines (U-138 and U-251) were infected with ZIKV at different multiplicities of infection (0.1, 0.01 and 0.001), and cell viability, migration, adhesion, induction of apoptosis, interleukin levels and CD14/CD73 cell surface marker expression were analyzed. The present study demonstrated that ZIKV infection promoted loss of cell viability and increased apoptosis in U-138 cells, as measured by MTT and triplex assay, respectively. Changes in cell migration, as determined by wound healing assay, were not observed; however, the GBM cell lines exhibited an increase in cell adhesion when compared with non-tumoral cells (Vero). The Luminex immunoassay showed a significant increase in the expression levels of IL-4 specifically in U-251 cells (MOI 0.001) following exposure to ZIKV. There was no significant change in the expression levels of IFN-γ upon ZIKV infection in the cell lines tested. Furthermore, a marked increase in the percentage of cells expressing the CD14 surface marker was observed in both GBM cell lines compared with in Vero cells; and significantly increased CD73 expression was observed particularly in U-251 cells, when compared with uninfected cells. These findings indicate that ZIKV infection could lead to reduced cell viability, elevated CD73 expression, improved cellular adherence, and higher rates of apoptosis in glioblastoma cells. Further studies are required to explore the potential use of ZIKV in the treatment of GBM.

Keywords: Zika virus; apoptosis; cell adhesion; glioblastoma; viral therapy.

Grants and funding

Funding was received from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (finance code 001) and Conselho Nacional de Desenvolvimento Científico e Tecnológico.