Transcription viral

Both amantadiae and rknantadiae have been found to reduce the duration of influenza A-iaduced fever and malaise, and to lessen viral shedding. Prophylactic treatment has been recommended for high risk patients (95). It has been suggested that, ia the presence of amantadine, the influenza vims attaches normally to cells, but once iaside the ceU the vims fails to initiate repHcation. Thus amantadine appears to inhibit the initiation of transcription at an early stage between uncoating and viral-specific RNA synthesis (96). 

Since the SUMO pathway affects multiple pathways ranging from transcription, DNA repair, and intracellular trafficking over cell signaling and cell cycle control to basic metabolism, it is not suiprising that links to diseases and viral assaults are emerging. However, the field is not yet at a stage sufficiently developed for pharmacological intervention. Below we will describe selected examples for links of the SUMO pathway to diseases and viral functions. 

Gough DJ, Sabapathy K, Ko EY, Arthur HA, Schreiber RD, Trapani JA, Clarke CJ, Johnstone RW (2007) A novel c-Jun-dependent signal transduction pathway necessary for the transcriptional activation of interferon gamma response genes. J Biol Chem 282 938-946 Guidotti LG, Chisari EV (2001) Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 19 65-91... 

Fig. 2 RNAi inducers used in antiviral strategies. In general, RNAi is induced either by transfection of synthetic siRNAs into cells, or by stable or transient intracellular expression of double-stranded siRNA precursors (shRNA, e-shRNA, IhRNA, or pri-miRNAs). After transcription in the nucleus shRNAs, IhRNAs and e-shRNAs are exported to the cytoplasm and subsequently diced into mature siRNAs. Pri-miRNAs modified to encode antiviral siRNAs first undergo cleavage by Drosha before they are exported to the cytoplasm. Here the antiviral pre-miRNAs (also called shRNA-miRs) are processed by Dicer into the mature miRNAs. After loading of the antisense strand of the siRNAs/miRNAs into RISC, the complex will target and cleave viral transcripts bearing the complementary sequences...

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