The human herpesvirus-8 ORF 57 gene and its properties

Human herpesvirus-8 (HHV-8) is a gamma(2) lymphotropic herpesvirus associat ed with Kaposi's sarcoma, a major neoplasm of AIDS patients, and with other AIDS-related neoplasms. The HHV-8 ORF 57 gene is conserved throughout the herpesvirus family and has a herpes simplex virus type 1 homologue, IE63 (a lso termed ICP27), which is an essential regulatory protein and acts at bot h transcriptional and post-transcriptional levels. We show that, contrary t o the published HHV-8 sequence, which predicts a protein of 275 amino acids , the ORF 57 gene is spliced, contains a single intron and encodes a protei n of 455 amino acids, For several gammaherpesviruses examined, the upstream coding exon is 16-17 amino acids in length and is rich in methionine resid ues. When ORF 57 was fused to the gene for enhanced green fluorescent prote in (EGFP), the fusion protein exhibited a punctate nuclear distribution tha t co-localized with the cellular splicing factor SC-35, Unlike the IE63-EGF P fusion protein, ORF 57-EGFP did not shuttle from the nucleus to the cytop lasm in the presence of actinomycin D, However, ORF 57-EGFP was capable of shuttling from a transfected monkey nucleus to a recipient mouse nucleus in an interspecies heterokaryon assay. These data indicate that HHV-8 ORF 57 and IE63 possess certain common properties.