Replication of Theiler's virus requires NF-κB-activation: Higher viral replication and spreading in astrocytes from susceptible mice

Min Hyung Kang, Eui Young So, Hyesuk Park, Byung S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

To investigate viral replication and cell-cell spreading in astrocytes, recombinant Theiler's murine encephalomyelitis virus (TMEV) expressing green fluorescent protein (GFP) during the replication was generated. GFP and TMEV proteins were processed correctly in infected cells and production of viral proteins could be tracked by fluorescent microscopy. Viral replication of both wild-type TMEV and GFP-TMEV was dependent on the activation of NF-κB and partially MAP kinase, based on chemical inhibition studies. Viral replication was significantly reduced in primary astrocytes from NF-κB1 (p105)-deficient mice compared with that from wild-type control mice, whereas cytokine production was enhanced. These results suggest an association of canonical NF-κB subunits in viral replication, but not cytokine production. Viral replication was also suppressed in both IKKα and IKKβ-deficient mouse embryonic fibroblasts (MEFs), compared with that in wild-type MEF. However, the inhibition was significantly greater in IKKβ-deficient MEF, suggesting that IKKβ plays a stronger role in supporting viral replication. Interestingly, viral replication and spreading in primary astrocytes from susceptible SJL/J mice were several-fold higher than those in astrocytes from resistant C57BL/6 mice, suggesting that higher viral replication levels in astrocytes may also contribute to the viral persistence in the central nervous system (CNS) of susceptible SJL/J mice. A relatively higher level of activated NF-κB was found in the nuclei of virus-infected SJL astrocytes compared with C57BL/6 astrocytes suggest that the NF-κB activation level affects on viral replication.

Original languageEnglish (US)
Pages (from-to)942-953
Number of pages12
JournalGlia
Volume56
Issue number9
DOIs
StatePublished - Jul 2008

Keywords

  • Astrocytes
  • NF-κB
  • TMEV
  • Viral replication
  • Viral spreading

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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