The open reading frame 57 gene product of herpesvirus saimiri shuttles between the nucleus and cytoplasm and is involved in viral RNA nuclear export

The herpesvirus saimiri open reading frame (ORF) 57 is homologous to genes identified in all classes of herpesviruses. It has previously been shown to regulate gene expression through a posttranscriptional mechanism. We demon strate in this report that the expression of the ORF 57 protein leads to th e cytoplasmic accumulation of glycoprotein B and capsid mRNAs. We also demo nstrate that ORF 57 has the ability to specifically bind viral RNA transcri pts. Utilizing an interspecies heterokaryon assay, we show that ORF 57 has the ability to shuttle between the nucleus and the cytoplasm. Furthermore, we show that ORF 57 contains a relatively leucine-rich sequence which share s some homology with nuclear export signals (NES) found in a number of prot eins with the ability to shuttle between the nucleus and the cytoplasm. Mor eover? we demonstrate that the ORF 57 NES enables the nuclear export of a h eterologous protein and that mutation of the conserved leucine residues con tained within the ORF 57 NES signal abrogates the ability of the ORF 57 pro tein to shuttle between the nucleus and cytoplasm. These results suggest th at ORF 57 is involved in mediating the nuclear export of viral transcripts.