Properties of an HSV-1 regulatory protein that appears to impair host cell splicing.
The herpes simplex virus type 1 (HSV-1) immediate early (alpha) protein ICP27 is an essential regulatory protein that appears to be involved in a number of different processes during lytic viral infection. Viral mutants defective in ICP27 have a variety of phenotypes that include defects in the shutoff of host protein synthesis, overexpression of some immediate early and early genes, reduced levels of DNA replication, and severely reduced levels of late gene products. ICP27 has been shown to act posttranscriptionally in the performance of some of its regulatory roles. It affects mRNA processing at the level of both polyadenylation and splicing. During polyadenylation, ICP27 appears to stimulate 3' RNA processing at selected poly(A) sites. The opposite effect, occurs on host cell splicing, that is, during HSV-1 infection, an inhibition in host cell splicing was found that required ICP27 expression. This impairment of splicing contributes to the shutoff of host protein synthesis by decreasing levels of spliced cellular mRNAs available for translation. A redistribution of splicing factors regulated by ICP27 has also been seen. Mutational analysis has shown that the C-terminal repressor region of the protein is required for the effects seen on splicing, whereas the activator region, encompassing the C-terminal half of the protein is required for the effects on 3' processing and the induction of late gene expression during viral infection. A highly basic arginine-rich region in the N-terminal half of the protein is required for nuclear localization of ICP27. Details on the mechanisms by which ICP27 contributes to these regulatory processes have been poorly defined to date.
Sandri-Goldin
R M
RM
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717-4025.
D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D011061:Poly A / Q000378:metabolism; D012326:RNA Splicing; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*
C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D011061:Poly A