Adams B, Zwernik SD, Kassam AB, Rovin RA, Akhtar P. Evaluation of Sox2 expression in glioblastoma stem cells during zika virus infection. Poster presented at: Aurora Scientific Day; May 22, 2019; Milwaukee, WI.
Poster presented at: Aurora Scientific Day; May 22, 2019; Milwaukee, WI.
Background: Glioblastoma is a deadly form of brain cancer. Standard treatment involves surgery followed by chemotherapy and radiation. Most tumors recur within 6 months, fueled by a small population of glioblastoma stem cells (GSCs) that resist and survive treatment. There are no pharmacological agents currently available for specific targeting of GSCs. Zika virus (ZIKV) is a flavivirus and is linked to congenital microcephaly in addition to other neurological manifestations. It appears that ZIKV selectively targets normal neural stem cells in the developing brain, causing the microcephaly. The specificity is due to receptor-mediated cell entry: a tyrosine kinase receptor, AXL, present on neural stem cells, specifically binds ZIKV and permits cell entry. We examined the effect of ZIKV on Sox2, a transcription factor that controls the self-renewal of stem cells.
Purpose: The purpose of this study is to understand the role of Sox2 in ZIKV infection in glioblastoma cancer stem cells.
Methods: ZIKV strain MR766 was propagated in Vero cells. Viral stock was titrated by plaque assays. Glioblastoma patientderived cell lines were infected with ZIKV, and the percentage of infected cells was quantified by flow cytometry using a pan-flavivirus antibody. Western blot was used to characterize Sox2 expression in 5 glioblastoma patient-derived cell lines. Immunofluorescence microscopy was used to visualize Sox2 levels after ZIKV infection.
Results: We found that Sox2 expression varies among the glioblastoma patient-derived cell lines (7754, 7730, 7714, 7753, and 7978) and is inversely correlated with AXL expression. We further found that ZIKV infection inhibits Sox2 levels in a dose-dependent manner in all 5 glioblastoma cell lines.
Conclusion: Our results suggest that ZIKV infection causes loss of self-renewal through Sox2 in glioblastoma cancer stem cells.