TNF-α stimulates efficient JC virus replication in neuroblastoma cells.

JC polyomavirus (JCV) causes progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS) in immunocompromised patients, and particularly in the severe immunosuppression associated with acquired immunodeficiency syndrome (AIDS). HIV-1 can lead to the production of tumor necrosis factor-alpha (TNF-) in the CNS. Our aim was to examine the effects of TNF- on JCV gene expression and replication using a human neuroblastoma cell line, IMR-32, transfected with JCV DNA, M1-IMRb. Quantitative RT-PCR analysis of JCV large T antigen and VP1 mRNA, the viral DNA replication assay, and the DNase protection assay were carried out. TNF- treatment of IMR-32 cells transfected with JCV DNA induced large T antigen mRNA and JCV DNA replication, while other effects on VP1 mRNA expression and virus production were marginal. In addition, ELISA analysis of the nuclear p65 subunit of nuclear factor B (NF-B), which is a hallmark of NF-B pathway activation, of IMR-32 cells upon TNF- treatment showed that TNF- treatment activated the NF-B pathway in IMR-32 cells. Taken together, our results suggest that TNF- stimulation could induce JCV replication associated with the induction of JCV large T antigen mRNA through the NF-B pathway in IMR-32 cells transfected with JCV DNA. Our findings may contribute to further understanding of the pathogenesis of AIDS-related PML. J. Med. Virol. 86:2026-2032, 2014. (c) 2014 Wiley Periodicals, Inc.