[Frontiers in Bioscience 5241-5256, May 1, 2008]

The many roles of the regulatory protein ICP27 during herpes simplex virus infection

Rozanne M. Sandri-Goldin

Department of Microbiology and Molecular Genetics, School of Medicine, University of California at Irvine, Irvine, CA 92697-4025 USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Post-transcriptional activities of ICP27
3.1. Pre-mRNA splicing inhibition
3.2. The role of ICP27 in 3' end formation
3.3. ICP27 and the export of viral mRNA
3.4. A role for ICP27 in translation
4. Transcriptional stimulation of HSV-1 expression by ICP27
4.1. ICP27 associates with RNA polymerase II
4.2. ICP27 recruits RNA polymerase II to viral replication sites
4.3. Elongating RNAP II is degraded during HSV-1 infection
5. Hsc70 nuclear focus formation requires ICP27
6. ICP27 directs many activities during infection
7. Regulation of ICP27's activities throughout Infection
7.1. Post-translation modifications: arginine methylation
7.2. Post-translational modifications: phosphorylation
8. The Domains required for the multiple interactions of ICP27
8.1. RNA binding by ICP27 confers some structural rigidity
8.2. Intramolecular interaction of the N- and C-termini of ICP27
9. Perspectives
10. Acknowledgments
11. References

1. ABSTRACT

Herpes simplex virus type 1 (HSV-1) protein ICP27 is a multifunctional regulator of gene expression that assumes different roles during the course of infection. Early in infection, ICP27 mediates the inhibition of cellular splicing, whereas, later it helps to recruit cellular RNA polymerase II (RNAP II) to viral replication sites and to facilitate viral RNA export. ICP27 has also been shown to stimulate translation of viral transcripts. ICP27 performs its activities by interacting with RNA and with an assortment of proteins. ICP27 binds viral RNAs in its role as an export adaptor. An ever increasing number of cellular proteins have been shown to interact with ICP27, including splicing factors, export proteins and RNAP II. A number of protein motifs within ICP27 have been predicted based upon sequence comparisons; however, detailed structural information is not yet available. 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.