HERPES SIMPLEX VIRUS GENE REGULATION
Principal Investigator: Rozanne M Sandri-Goldin
Affiliation: University of California
Abstract: Herpes simplex virus type 1 (HSV-1) undergoes two types of interaction with host cells, lytic infection and latent infection. During lytic growth, following primary exposure or reactivation, HSV-1 can cause a wide spectrum of human diseases. On the other hand, the virus can remain latent in the trigeminal ganglia of infected individuals for years. Little is known about the viral or cellular functions required for maintenance of the latent state or for reactivation. The regulation of HSV-1 gene expression during lytic infection in tissue culture is a complex and highly coordinated process. At least three classes of genes are expressed in a sequential fashion. The order of expression is mediated in part by the action of viral encoded trans-acting proteins on specific sequences in the promoter-regulatory domains of HSV-1 genes. To elucidate the mechanism of action of two of these trans-acting proteins, a detailed genetic and biochemical analysis will be performed on the alpha proteins, ICP27 and ICP0. ICP27 is required for late gene expression during infection. ICP0 also affects late gene expression although not to the extent that ICP27 does. In transfection assays, both proteins affect the expression of HSV-1 genes and heterologous genes but do so differently. ICP0 stimulates expression while ICP27 negatively regulates expression. To examine whether these proteins function by direct DNA interactions or indirectly through interactions with other transcription proteins, ICP27 and ICP0 will be purified. The specificity and affinity of binding to DNA will be analyzed. Protein-protein interactions will be investigated by immuno- affinity chromatography and protein affinity chromatography. The purified proteins will also be assayed for putative enzymatic functions by which they could modify other transcriptional proteins. To correlate activities of each protein with specific domains, a series of in-frame insertion mutations will be introduced into the ICP27 and ICP0 genes. Mutant proteins will be isolated and analyzed to determine which functions or activities are affected. In this way, a functional map of each protein can be derived.
Funding Period: 1984-07-01 - 1992-06-30
more information: NIH RePORT
- ICP27 recruits Aly/REF but not TAP/NXF1 to herpes simplex virus type 1 transcription sites although TAP/NXF1 is required for ICP27 exportI Hsiung Brandon Chen
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, CA 92697 4025, USA
J Virol 79:3949-61. 2005..Therefore, the interaction of ICP27 with TAP/NXF1 occurs after ICP27 leaves viral transcription sites. We conclude that ICP27 and the viral RNAs to which it binds are exported via the TAP/NXF1 export receptor...
- ICP27 interacts with the C-terminal domain of RNA polymerase II and facilitates its recruitment to herpes simplex virus 1 transcription sites, where it undergoes proteasomal degradation during infectionJenny Q Dai-Ju
Department of Microbiology and Molecular Genetics, School of Medicine, University of California at Irvine, Irvine, CA 92697 4025, USA
J Virol 80:3567-81. 2006..Thus, we propose that at later times of infection when robust transcription and DNA replication are occurring, elongating complexes may collide and proteasomal degradation may be required for resolution...
- The many roles of the regulatory protein ICP27 during herpes simplex virus infectionRozanne M Sandri-Goldin
Department of Microbiology and Molecular Genetics, School of Medicine, University of California at Irvine, Irvine, CA 92697 4025 USA
Front Biosci 13:5241-56. 2008..Although much has been learned about the mechanisms by which ICP27 performs its roles, relatively little is known about how its activities are regulated. The roles and activities of ICP27 are the subject of this review...
- Arginine methylation of the ICP27 RGG box regulates ICP27 export and is required for efficient herpes simplex virus 1 replicationStuart K Souki
Department of Microbiology and Molecular Genetics, School of Medicine, Medical Sciences, University of California, Irvine, CA 92697 4025, USA
J Virol 83:5309-20. 2009..We conclude that arginine methylation of the ICP27 RGG box regulates its export activity and that early export of ICP27 interferes with the performance of its nuclear functions...
- The HSV-1 ICP27 RGG box specifically binds flexible, GC-rich sequences but not G-quartet structuresKara A Corbin-Lickfett
Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, CA 92697, USA
Nucleic Acids Res 37:7290-301. 2009..Therefore, the ICP27 RGG box is unique in its recognition of nucleic acid sequences compared to other RGG box proteins; it prefers flexible, GC-rich substrates that do not form stable secondary structures...