SHUTTLING OF THE HERPES-SIMPLEX VIRUS TYPE-1 REGULATORY PROTEIN ICP27BETWEEN THE NUCLEUS AND CYTOPLASM MEDIATES THE EXPRESSION OF LATE PROTEINS

The herpes simplex virus type 1 (HSV-1) immediate-early protein ICP27 is required posttranscriptionally for the expression of HSV-1 late gen es during a productive infection. ICP27 also inhibits host cell pre-mR NA splicing, effectively shutting off host cell protein synthesis. Her e we describe intragenic suppressors of LG4, a virus with a conditiona l lethal mutation in the gene encoding ICP27. At the restrictive tempe rature, tsICP27 from LG4 fails to inhibit host cell pre-mRNA splicing and to activate the expression of HSV-1 late-gene products. Although t he suppressors of LG4 restore virus growth, they still fail to inhibit host cell pre mRNA splicing. Thus, the role of ICP27 in the synthesis of late proteins is independent of host shutoff. In HSV-1-infected ce lls, ICP27 shuttles between the nucleus and the cytoplasm. Shuttling o f ICP27 occurs only at late times during infection. In transfected cel ls, ICP27 shuttling was dependent on coexpression of RNA from a late H SV-1 gene. While shuttling does not occur in cells infected with LG4 a t 39.5 degrees C, the suppressors of LG4 restore shuttling. Temperatur e shift experiments correlate the defect in shuttling with the tempera ture-sensitive phenotype of LG4. These data provide a correlation betw een shuttling of ICP27 and the expression of HSV-1 late gene products. We propose that ICP27 regulates late-gene protein synthesis by facili tating the export of late RNAs.