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 language | English (US) |
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Pages (from-to) | 942-953 |
Number of pages | 12 |
Journal | Glia |
Volume | 56 |
Issue number | 9 |
DOIs | |
State | Published - Jul 2008 |
Keywords
- Astrocytes
- NF-κB
- TMEV
- Viral replication
- Viral spreading
ASJC Scopus subject areas
- Neurology
- Cellular and Molecular Neuroscience