HERPES-SIMPLEX-VIRUS-1 REGULATORY PROTEIN ICP22 INTERACTS WITH A NEW CELL-CYCLE-REGULATED FACTOR AND ACCUMULATES IN A CELL CYCLE-DEPENDENT FASHION IN INFECTED-CELLS

The herpes simplex virus I infected cell protein 22 (ICP22), the produ ct of the alpha 22 gene, is a nucleotidylylated and phosphorylated nuc lear protein with properties of a transcriptional factor required for the expression of a subset of viral genes. Here, we report the followi ng, (i) ICP22 interacts with a previously unknown cellular factor desi gnated p78 in the yeast two-hybrid system. The p78 cDNA encodes a poly peptide with a distribution of leucines reminiscent of a leucine zippe r. (ii) In uninfected and infected cells, antibody to p78 reacts with two major bands with an apparent M-r of 78,000 and two minor bands wit h apparent M(r)s of 62,000 and 55,000. (ii) p78 also interacts with IC P22 in vitro. (iii) In uninfected cells, p78 was dispersed largely in the nucleoplasm in HeLa cells and in the nucleoplasm and cytoplasm in HEp-2 cells. After infection, p78 formed large dense bodies which did not colocalize with the viral regulatory protein ICP0, (iv) Accumulati on of p78 was cell cycle dependent, being highest very early in S phas e. (v) The accumulation of ICP22 in synchronized cells was highest in early S phase, in contrast to the accumulation of another protein, ICP 27, which was relatively independent of the cell cycle. (vi) In the co urse of the cell cycle, ICP22 was transiently modified in an aberrant fashion, and this modification coincided with expression of p78, The r esults suggest that ICP22 interacts with and may be stabilized by cell cycle-dependent proteins.