A study was undertaken to compare the efficacy of plasmid constructs encoding human IFN-alpha 2 and IFN-beta and macaque IFN-beta against herpes simplex virus type 1 in transfected cells. All type I IFN transgenes significantly reduced viral titers in transfected cells by 3 logs. Human IFN-alpha 2-transfected cells produced significantly more IFN (2274 pg/ml) in comparison to IFN-beta-transfected cells (134-165 pg/ml). Viral lytic gene transcript and viral protein levels were lower in IFN-beta- versus IFN-alpha 2-transfected cells, which coincided with elevated PKR and OAS transcript levels and increased total STAT1 and phosphorylated STAT1 (Y701) protein levels in the IFN-beta-transfected cells. Although comparable viral titers were recovered in IFN-alpha 2 and IFN-beta plasmid-transfected cells, IFN-alpha 2 plasmid-transfected cells exhibited significantly more cytopathic effect compared to the IFN-beta transgene-transfected cells. In addition, IFN-alpha 2 transgene-transfected, infected cells displayed a cell cycle profile similar to that of vector-transfected, infected cells, whereas IFN-beta plasmid-transfected cells displayed a profile similar to uninfected control. Collectively, the results indicate that human IFN-beta is superior to IFN-alpha 2 in antagonizing herpes simplex virus type 1 infection.
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