EXTH-68. ZIKA VIRUS ONCOTROPISM TOWARDS GLIOBLASTOMA PROGENITOR CELLS IS MEDIATED BY THE TYROSINE KINASE RECEPTOR Axl
Year: 2018
Type: conference-abstract
Abstract: An oncolytic virus must display tropism for the target cancer. This oncotropism is mediated by cell surface receptors that are differentially expressed by the cancer cell. Recent research into the mechanism of Zika virus (ZV) induced microcephaly demonstrated that ZV has neurotropism for fetal neural progenitor cells, and this is mediated by Axl. Axl is a member of the TAM (Tyro3, Axl, Mer) family of tyrosine kinase receptors. Additional research showed that Axl is overexpressed in 60% of glioblastoma (GBM). We therefore hypothesized that ZV could target GBM progenitor cells through the Axl receptor. Using Western blot, we discovered that there is a range of Axl expression in commercially available cell lines (5 GBM, 2 breast cancer) and in 11 patient derived GBM progenitor cell lines. Using flow cytometry and immunofluorescence microscopy, we confirmed that ZV cell entry correlates with Axl expression. ZV did not enter nor productively infect Axl negative cell lines. While at 24 hours post exposure, the number of intracellular viral particles increased as Axl expression increased. We next demonstrated that ZV entry was abrogated by the Axl inhibitor R428 in a dose dependent manner, and, anti-Axl antibody treatment also prevented ZV entry. These findings were again confirmed with both flow cytometry and immunofluorescence microscopy. We therefore conclude that ZV is oncotropic towards GBM progenitor cells and this is mediated by the Axl receptor. Thus, ZV meets the first requirement for a GBM oncolytic virus: receptor mediated oncotropism.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2900225810