This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bourteele, S. Articles by Planz, O. Search for Related Content PubMed PubMed Citation Articles by Bourteele, S. Articles by Planz, O.

 Previous Article  |  Next Article 

Journal of Virology, May 2005, p. 6043-6051, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6043-6051.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Constitutive Activation of the Transcription Factor NF-B Results in Impaired Borna Disease Virus Replication

Institut für Immunologie, Friedrich-Loeffler-Institut Bundesforschungsinstitut für Tierkrankheiten, Tübingen, Germany,¹ Institut für Medizinische Virologie, FB 11, Justus-Liebig-Universität, Giessen, Germany,² Robert Koch Institut, Berlin, Germany,³ Institut für Molekulare Medizin (IMM), Heinrich-Heine Universität, Düsseldorf, Germany,⁴ Institut für Molekulare Virologie, Westfälische Wilhelms-Universität, Münster, Germany⁵

Received 13 August 2004/ Accepted 28 December 2004

The inducible transcription factor NF-B 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-B 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-B signaling pathway. While BDV titers were not affected in cells with impaired NF-B signaling, the expression of an activated mutant of IB 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-B 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-B 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-B preferentially spread to areas of the brains of infected rats where activated NF-B was not detectable.

This article has been cited by other articles:

• Unterstab, G., Ludwig, S., Anton, A., Planz, O., Dauber, B., Krappmann, D., Heins, G., Ehrhardt, C., Wolff, T. (2005). Viral targeting of the interferon-{beta}-inducing Traf family member-associated NF-{kappa}B activator (TANK)-binding kinase-1. Proc. Natl. Acad. Sci. USA 102: 13640-13645 [Abstract] [Full Text]