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

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Bourteele S,Oesterle K,Pleschka S,Unterstab G,Ehrhardt C,Wolff T,Ludwig S,Planz O

doi

10.1128/JVI.79.10.6043-6051.2005

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

6043-51

issue

10

eissn

0022-538X

issn

1098-5514

pii

79/10/6043

journal_volume

79

pub_type

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