A MAJOR TRANSACTIVATOR OF VARICELLA-ZOSTER VIRUS, THE IMMEDIATE-EARLYPROTEIN IE62, CONTAINS A POTENT N-TERMINAL ACTIVATION DOMAIN

Accumulating evidence indicates that the product of the putative immed iate-early gene ORF62 (IE62) activates varicella-zoster virus (VZV) ge nes thought to represent all three kinetic classes, namely, immediate- early (alpha), early (beta), and late (gamma) classes, of VZV genes as well as a variety heterologous gene promoters. However, the mechanism (s) by which IE62 protein mediates transactivation of these diverse VZ V and beterologous gene promoters remains to be elucidated. In this st udy, by using yeast GALA protein chimeras, the coding regions of VZV O RF62 possessing activation domains have been assessed. We demonstrate that the VZV IE62 protein contains a potent activation domain in the N -terminal portion of the molecule, encoded within the first 86 codons of ORF62. The predicted secondary structure profile and the acid-base composition of this IE62 domain resemble those of other transregulator y proteins whose activation is mediated through acidic, hydrophobic el ements. In addition, we show that deletion of this activation domain f rom the 1,310-residue native IE62 protein results in ablation of the t ransactivator function of IE62. We also present evidence that the muta nt IE62 protein lacking the activation domain, though devoid of transa ctivation ability, was still capable of interfering with the activatio n of target promoters by the native, full-length IE62.