Premium
TNF‐α stimulates efficient JC virus replication in neuroblastoma cells
Author(s) -
Nukuzuma Souichi,
Nakamichi Kazuo,
Kameoka Masanori,
Sugiura Shigeki,
Nukuzuma Chiyoko,
Tasaki Takafumi,
Takegami Tsutomu
Publication year - 2014
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.23886
Subject(s) - virology , virus , viral replication , replication (statistics) , tumor necrosis factor alpha , biology , immunology
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‐α) in the CNS. Our aim was to examine the effects of TNF‐α 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‐α 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 κB (NF‐κB), which is a hallmark of NF‐κB pathway activation, of IMR‐32 cells upon TNF‐α treatment showed that TNF‐α treatment activated the NF‐κB pathway in IMR‐32 cells. Taken together, our results suggest that TNF‐α stimulation could induce JCV replication associated with the induction of JCV large T antigen mRNA through the NF‐κB 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 . © 2014 Wiley Periodicals, Inc.