Juang Y T, Au W C, Lowther W, Hiscott J, Pitha P M
Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
J Biol Chem. 1999 Jun 18;274(25):18060-6. doi: 10.1074/jbc.274.25.18060.
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.
我们研究了脂多糖（LPS）对新城疫病毒（NDV）介导的细胞因子基因表达诱导的影响。在病毒感染之前或之后用LPS处理的Raw细胞显示，干扰素A的表达下调，而干扰素B基因的表达下调程度较小。相比之下，白细胞介素（IL）-6基因的诱导增强。LPS的作用并非是抑制病毒复制的结果，因为病毒核衣壳基因的转录未受影响。与这些发现一致，在瞬时转染试验中，LPS还抑制了由鼠干扰素A4启动子驱动的氯霉素乙酰转移酶报告基因的NDV介导的诱导。此外，LPS抑制病毒介导的干扰素调节因子（IRF）-3的磷酸化以及随后IRF-3从细胞质到细胞核的转运。在组成性过表达IRF-3的感染Raw细胞中，LPS介导的IFNA基因表达抑制作用要弱得多。LPS还抑制感染细胞中IRF-7的核转运。这些数据表明，LPS通过翻译后靶向IRF-3和IRF-7蛋白来下调病毒介导的IFNA基因诱导。
