JC Virus Induces Nonapoptotic Cell Death

JC virus (JCV), a human neurotropic polyomavirus, demonstrates a selective glial cell tropism that causes cell death through lytic infection. The objective of this study was to investigate the mechanism of virus-induced cell death in human central nervous system progenitor-derived astrocytes. We employed a cell culture model developed in our laboratory and utilized various methodologies, including in situ DNA hybridization, immunocytochemistry, electron microscopy, and RNase protection assays. Our findings revealed that infected astrocyte cell cultures showed no differences from noninfected cells in mRNA expression of caspase family genes or in any ultrastructural features associated with apoptosis. Instead, infected cells exhibited striking necrotic features such as cytoplasmic vacuolization, watery cytoplasm, and organelle dissolution. Additionally, staining for caspase-3 and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling were not detected in infected astrocyte cultures. Therefore, we conclude that JCV-induced cell death in these progenitor cell-derived astrocytes does not follow an apoptotic pathway, but rather presents a pattern of cell destruction characteristic of necrotic cell death.