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.

Abstract

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.

• Authors: P Härle, E Lauret, P M Pitha, E De Maeyer, D J Carr
• Journal: Virology (Virology) Vol. 290 Issue 2 Pg. 237-48 (Nov 25 2001) ISSN: 0042-6822 [Print] United States
• PMID: 11883188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA-Binding Proteins
• Herpes Simplex Virus Protein Vmw65
• ICP27 protein, human herpesvirus 1
• Immediate-Early Proteins
• Interferon-alpha
• RNA, Messenger
• STAT1 Transcription Factor
• STAT1 protein, human
• Stat1 protein, mouse
• Trans-Activators
• Interferon-beta
• Thymidine Kinase
• eIF-2 Kinase
• 2',5'-Oligoadenylate Synthetase

Topics

• 2',5'-Oligoadenylate Synthetase (genetics)
• Animals
• Apoptosis
• Chlorocebus aethiops
• DNA-Binding Proteins (metabolism)
• Gene Expression
• Gene Expression Regulation, Viral
• Herpes Simplex Virus Protein Vmw65 (genetics)
• Herpesvirus 1, Human (genetics, physiology)
• Humans
• Immediate-Early Proteins (genetics)
• Interferon-alpha (biosynthesis, genetics)
• Interferon-beta (biosynthesis, genetics)
• Macaca
• Mice
• Protein Biosynthesis
• RNA, Messenger (metabolism)
• STAT1 Transcription Factor
• Thymidine Kinase (genetics)
• Time Factors
• Trans-Activators (metabolism)
• Transcription, Genetic
• Transfection
• Transgenes
• Tumor Cells, Cultured
• Vero Cells
• Virus Replication (physiology)
• eIF-2 Kinase (genetics)