Expression of human and macaque type I IFN transgenes interferes with HSV-1 replication at the transcriptional and translational levels: IFN-beta is more potent than IFN-alpha 2.
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.
Härle
P
P
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Lauret
E
E
Pitha
P M
PM
De Maeyer
E
E
Carr
D J
DJ
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008251:Macaca; D051379:Mice; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor; D013937:Thymidine Kinase / Q000235:genetics; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*; D019892:eIF-2 Kinase / Q000235:genetics
D004268:DNA-Binding Proteins; D017405:Herpes Simplex Virus Protein Vmw65; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D016899:Interferon-beta; D013937:Thymidine Kinase; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase