EXPRESSION OF TRANSCRIPTION FACTOR GENES AFTER INFLUENZA-A VIRUS-INFECTION

Infection of human monocytes with influenza A virus induces a broad ra nge of proinflammatory cytokines and mononuclear cell attracting chemo kines before the infected cells undergo apoptosis. The underlying mech anisms by which the corresponding genes are transcriptionally initiate d after virus infection are still poorly understood. Activation of NF- kappa B seems to play an important role in the regulation of many proi nflammatory cytokine genes, but cannot be the only mechanism, since se veral cytokine genes lack respective binding sites in their promoter r egions. Therefore, we additionally investigated other transcription fa ctors of possible importance such as CREB, CTF, OTF-1, and OTF-2. To e xplore long-term regulatory mechanisms, we investigated the induction of transcription factors on the gene expression level which may be imp ortant to substitute for metabolized transcription factor proteins aft er their activation. We identified a cell-type-specific differential r esponse: CREB, CTF, OTF-1, OFT-2, and NF-kappa B genes were strongly i nduced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6, while in freshly prepared human monocytes no si gnificant changes were detected. In infected monocytes, which die by a poptosis, the expression of CREB, CTF, and OTF-2 was rather suppressed 8 hours after infection. In conclusion, the long-term regulation of t ranscription factor gene expression in nonproliferating cells seems to be of minor importance after influenza infection since in apoptosispr one cells an immediate availability of transcription factor proteins i s required.