Kaposi's sarcoma-associated herpesvirus open reading frame 57 encodes a posttranscriptional regulator with multiple distinct activities

Open reading frame (ORF) 57 of Kaposi's sarcoma-associated herpesvirus (KSH V) encodes a homolog of known posttranscriptional regulators that are essen tial for replication in other herpesviruses. Here, we examined the expressi on of this gene and the function(s) of its product. KSHV ORF 57 is expresse d very early in infection from a 1.6-kb spliced RNA bearing several in-fram e initiation codons. Its product is a nuclear protein that, in transient as says, has little effect on the expression of luciferase reporter genes driv en by a variety of KSHV and heterologous promoters. However, ORF 57 protein enhances the accumulation of several viral transcripts, in a manner sugges ting posttranscriptional regulation. These transcripts include not only kno wn cytoplasmic mRNAs (e.g., ORF 59) but also a nuclear RNA (nut-l) that lac ks coding potential. Finally, ORF 57 protein can also modulate the effects of the ORF 50 gene product, a classical transactivator known to be required for lytic induction. The expression from some (e.g., nut-1) but not all (e .g., tk) ORF 50-responsive promoters can be synergistically enhanced by coe xpression of ORF 50 and ORF 57. This effect is not due to upregulation of O RF 50 expression but rather to a posttranslational enhancement of the trans criptional activity of ORF 50. These data indicate that ORF 57 is a powerfu l pleiotropic effector that can act on several posttranscriptional levels t o modulate the expression of viral genes in infected cells.