Lipopolysaccharide inhibits virus-mediated induction of interferon genes by disruption of nuclear transport of interferon regulatory factors 3 and 7

We have studied the effects of lipopolysaccharide (LPS) on the Newcastle di sease virus (NDV)-mediated induction of cytokine genes expression. Raw cell s treated with LPS before or after virus infection showed down-regulation i n the expression of interferon A and, to a lesser extent, interferon B gene s. 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, b ecause the transcription of viral nucleocapsid gene was not affected. Consi stent with these findings, LPS also suppressed the NDV-mediated induction o f chloramphenicol acetyltransferase reporter gene driven by murine interfer on A4 promoter in a transient transfection assay. Furthermore, LPS-inhibite d virus-mediated phosphorylation of interferon regulatory factor (IRF)-3 an d 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-5. The nuclear translocation o f IRF-7 in infected cells was also inhibited by LPS. These data suggest tha t LPS down-regulates the virus-mediated induction of IFNA genes by post-tra nslationally targeting the IRF-3 and IRF-7 proteins.