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J Biol Chem, Vol. 274, Issue 25, 18060-18066, June 18, 1999
From the We have studied the effects of lipopolysaccharide
(LPS) on the Newcastle disease virus (NDV)-mediated induction of
cytokine genes expression. Raw cells treated with LPS before or after
virus infection showed down-regulation in the expression of interferon A and, to a lesser extent, interferon B genes. In contrast, induction of the interleukin (IL)-6 gene was enhanced. The effects of LPS were
not a result of the suppression of virus replication, because the
transcription of viral nucleocapsid gene was not affected. Consistent
with these findings, LPS also suppressed the NDV-mediated induction of
chloramphenicol acetyltransferase reporter gene driven by murine
interferon A4 promoter in a transient transfection assay. Furthermore,
LPS inhibited virus-mediated phosphorylation of interferon regulatory
factor (IRF)-3 and the consequent translocation of IRF-3 from cytoplasm
to nucleus. The LPS-mediated inhibition of IFNA gene expression was
much weaker in infected Raw cells that constitutively overexpressed
IRF-3. The nuclear translocation of IRF-7 in infected cells was also
inhibited by LPS. These data suggest that LPS down-regulates the
virus-mediated induction of IFNA genes by post-translationally
targeting the IRF-3 and IRF-7 proteins.
Lipopolysaccharide Inhibits Virus-mediated Induction of
Interferon Genes by Disruption of Nuclear Transport of Interferon
Regulatory Factors 3 and 7
,,,¶
Oncology Center and the ¶ Department of
Molecular Biology & Genetics, The Johns Hopkins University School of
Medicine, Baltimore, Maryland 21231 and the § Lady Davis
Institute for Medical Research, Department of Microbiology & Medicine,
McGill University, Montreal, Quebec H3T 1E2, Canada
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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