Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Virol. 2005 May;79(10):6043-51.

Constitutive activation of the transcription factor NF-kappaB results in impaired borna disease virus replication.

Author information

  • 1Institut für Immunologie, Friedrich Loeffler Institut, Bundesforschungsinstitut für Tiergesundheit, Paul Ehrlich Str. 28, 72076 Tübingen, Germany.

Abstract

The inducible transcription factor NF-kappaB is commonly activated upon RNA virus infection and is a key player in the induction and regulation of the innate immune response. Borna disease virus (BDV) is a neurotropic negative-strand RNA virus, which replicates in the nucleus of the infected cell and causes a persistent infection that can lead to severe neurological disorders. To investigate the activation and function of NF-kappaB in BDV-infected cells, we stably transfected the highly susceptible neuronal guinea pig cell line CRL with a constitutively active (IKK EE) or dominant-negative (IKK KD) regulator of the IKK/NF-kappaB signaling pathway. While BDV titers were not affected in cells with impaired NF-kappaB signaling, the expression of an activated mutant of IkappaB kinase (IKK) resulted in a strong reduction in the intracellular viral titer in CRL cells. Electrophoretic mobility shift assays and luciferase reporter gene assays revealed that neither NF-kappaB nor interferon regulatory factors (IRFs) were activated upon acute BDV infection of wild-type or vector-transfected CRL cells. However, when IKK EE-transfected cells were used as target cells for BDV infection, DNA binding to an IRF3/7-responsive DNA element was detectable. Since IRF3/7 is a key player in the antiviral interferon response, our data indicate that enhanced NF-kappaB activity in the presence of BDV leads to the induction of antiviral pathways resulting in reduced virus titers. Consistent with this observation, the anti-BDV activity of NF-kappaB preferentially spread to areas of the brains of infected rats where activated NF-kappaB was not detectable.

PMID:
15857990
[PubMed - indexed for MEDLINE]
PMCID:
PMC1091684
Free PMC Article

Images from this publication.See all images (5)Free text

FIG. 1.
FIG. 2.
FIG. 3.
FIG. 4.
FIG. 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk