Role of Cellular Phosphatase cdc25C in Herpes Simplex Virus 1 Replication

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Abstract
Earlier studies have shown that in herpes simplex virus 1-infected cells, ICP22 upregulates the accumulation of a subset of γ 2 proteins exemplified by the products of the U L 38, U L 41, and U S 11 genes. The ICP22-dependent process involves degradation of cyclins A and B1, the stabilization and activation of cdc2, physical interaction of activated cdc2 with the U L 42 DNA synthesis processivity factor, and recruitment and phosphorylation of topoisomerase IIα by the cdc2/U L 42 complex. Activation of cdc2, the first step in the process, is a key function of the mitotic phosphatase cdc25C. To define the role of cdc25C, we probed some features of the ICP22-dependent pathway of upregulation of γ 2 genes in cdc25C −/− cells and in cdc25C +/+ cells derived from sibling mice. We report that cyclin B1 turned over in cdc25C +/+ or cdc25C −/− cells at the same rate, that cdc2 increased in amount, and that U S 11 and U L 38 proteins and infectious virus accumulated in smaller amounts than in wild-type infected cells. The reduction in U L 38 protein accumulation and virus was greater in cdc25C −/− cells infected with virus lacking ICP22 than in cells infected with wild-type virus. We conclude that cdc25C phosphatase plays a role in viral replication and that this role extends beyond its function of activating cdc2 for initiation of the ICP22-dependent cascade for upregulation of γ 2 gene expression.

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