title: Replication of Theiler's virus requires NF-kappa B-activation: higher viral replication and spreading in astrocytes from susceptible mice.
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-kappaB and partially MAP kinase, based on chemical inhibition studies. Viral replication was significantly reduced in primary astrocytes from NF-kappaB1 (p105)-deficient mice compared with that from wild-type control mice, whereas cytokine production was enhanced. These results suggest an association of canonical NF-kappaB subunits in viral replication, but not cytokine production. Viral replication was also suppressed in both IKKalpha and IKKbeta-deficient mouse embryonic fibroblasts (MEFs), compared with that in wild-type MEF. However, the inhibition was significantly greater in IKKbeta-deficient MEF, suggesting that IKKbeta 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-kappaB was found in the nuclei of virus-infected SJL astrocytes compared with C57BL/6 astrocytes suggest that the NF-kappaB activation level affects on viral replication.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: Min Hyung
authors.initials: MH
authors.lastname: Kang
authors.forename: Eui Young
authors.initials: EY
authors.lastname: So
authors.forename: Hyesuk
authors.initials: H
authors.lastname: Park
authors.forename: Byung S
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000821:virology*; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D017945:Theilovirus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
chemical_list: D016328:NF-kappa B