HYDROPHOBIC CLUSTER-ANALYSIS PREDICTS AN AMINO-TERMINAL DOMAIN OF VARICELLA-ZOSTER VIRUS OPEN-READING-FRAME-10 REQUIRED FOR TRANSCRIPTIONALACTIVATION

Varicella-zoster virus open reading frame 10 (ORF10) protein, the homo log of the herpes simplex virus protein VP16, fan transactivate immedi ate-early promoters from both viruses. A protein sequence comparison p rocedure termed hydrophobic cluster analysis was used to identify a mo tif centered at Phe-28, near the amino terminus of ORF10, that strongl y resembles the sequence of the activating domain surrounding Phe-442 of VP16. With a series of GAL4-ORF10 fusion proteins, we mapped the OR F10 transcriptional-activation domain to the amino-terminal region (aa 5-79). Extensive mutagenesis of Phe-28 in GAL4-ORF10 fusion proteins demonstrated the importance of an aromatic or bulky hydrophobic amino acid at this position, as shown previously for Phe-442 of VP16. Transa ctivation by the native ORF10 protein was abolished when Phe-28 was re placed by Ala. Similar amino-terminal domains were identified in the V P16 homologs of other alphaherpesviruses. Hydrophobic cluster analysis correctly predicted activation domains of ORF10 and VP16 that share c ritical characteristics of a distinctive subclass of acidic activation domains.