ROLE OF OXIDANTS IN INFLUENZA VIRUS-INDUCED GENE-EXPRESSION

Influenza virus-induced epithelial damage may be mediated, in part, by reactive oxygen intermediates (ROIs). In this study, we investigated the role of ROIs in the influenza virus-induced gene expression of ant ioxidant enzymes and in the activation of nuclear factor-kappa B (NF-k appa B), an oxidant-sensitive transcriptional factor. Influenza virus infection increased production of intracellular ROIs in A549 pulmonary epithelial cells. Induction of manganese superoxide dismutase (MnSOD) mRNA correlated with increased MnSOD protein and enzyme activity. Inf luenza virus infection also activated NF-(kappa) B binding as determin ed by an electrophoretic mobility shift assay. Pretreatment of A549 ce lls with N-acetyl-L-cysteine attenuated virus-induced NF-kappa B activ ation and interleukin (IL)-8 mRNA. induction but did not block inducti on of MnSOD mRNA. In contrast, pyrrolidine dithiocarbamate blocked act ivation of NF-kappa B and induction of MnSOD and IL-8 mRNAs. Treatment with pyrrolidine dithiocarbamate also markedly decreased virus-induce d cell death. Thus oxidants are involved in influenza virus-induced ac tivation of NF-kappa B, in the expression of IL-8 and MnSOD, and in vi rus-induced cell death.