Herpes Simplex virus type I (HSV-1) infects a wide variety of animals, tissues and cultured cells and established life long latent infections in the sensory neurons of the host. HSV-1 has the ability to completely overtake the host cell gene expression machinery for its own replication during infection. The HSV-1 ICP27 protein is an important mediator of this gene expression conversion within the infected cell. ICP27 binds HSV-1 mRNA and several viral and cellular proteins to promote viral gene expression. However, the regions required of ICP27 required for these interactions have been broadly mapped and there is no structural information for ICP27. The purpose of Aim 1 is to determine the structure of the predicted ICP27 C-terminal protein binding domain using NMR analysis.
In Aim 2, the ICP27 structural motifs will be specifically mutated to inactivate the structure of each domain and determine the effect on 1CP27 functions during HSV-1.
In Aim 3, ICP27 protein complexes will be isolated and purified and analyzed by Mass Spectrometry in order to identify novel protein interactions. This study will elucidate the structure of the ICP27 functional domains and chart the complete array of its dynamic interactions during infection.
| Corbin-Lickfett, Kara A; Rojas, Santos; Li, Ling et al. (2010) ICP27 phosphorylation site mutants display altered functional interactions with cellular export factors Aly/REF and TAP/NXF1 but are able to bind herpes simplex virus 1 RNA. J Virol 84:2212-22 |
| Corbin-Lickfett, Kara A; Souki, Stuart K; Cocco, Melanie J et al. (2010) Three arginine residues within the RGG box are crucial for ICP27 binding to herpes simplex virus 1 GC-rich sequences and for efficient viral RNA export. J Virol 84:6367-76 |
| Corbin-Lickfett, Kara A; Chen, I-Hsiung Brandon; Cocco, Melanie J et al. (2009) The HSV-1 ICP27 RGG box specifically binds flexible, GC-rich sequences but not G-quartet structures. Nucleic Acids Res 37:7290-301 |
