This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02021-07v1 82/9/4527    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Google Scholar Articles by Smith-Donald, B. A. Articles by Roizman, B. PubMed PubMed Citation Articles by Smith-Donald, B. A. Articles by Roizman, B.

Role of Cellular Phosphatase cdc25C in Herpes Simplex Virus 1 Replication

Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, Illinois 60637

Received 13 September 2007/ Accepted 5 February 2008

Earlier studies have shown that in herpes simplex virus 1-infected cells, ICP22 upregulates the accumulation of a subset of ₂ proteins exemplified by the products of the U_L38, U_L41, and U_S11 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_L42 DNA synthesis processivity factor, and recruitment and phosphorylation of topoisomerase II by the cdc2/U_L42 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 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_S11 and U_L38 proteins and infectious virus accumulated in smaller amounts than in wild-type infected cells. The reduction in U_L38 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 ₂ gene expression.

Published ahead of print on 13 February 2008.

This article has been cited by other articles:

• Smith-Donald, B. A., Roizman, B. (2008). The Interaction of Herpes Simplex Virus 1 Regulatory Protein ICP22 with the cdc25C Phosphatase Is Enabled In Vitro by Viral Protein Kinases US3 and UL13. J. Virol. 82: 4533-4543 [Abstract] [Full Text]